Skip to main content
SpringerLink
Log in

Wiring and Volume Transmission in Rat Amygdala. Implications for Fear and Anxiety

  • Overview
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The amygdala plays a key role in anxiety. Information from the environment reaches the amygdaloid basolateral nucleus and after its processing is relayed to the amygdaloid central nucleus where a proper anxiogenic response is implemented. Experimental evidence indicates that in this information transfer a GABAergic interface controls the trafficking of impulses between the two nuclei. Recent work indicates that interneuronal communication can take place by classical synaptic transmission (wiring transmission) and by volume transmission in which the neurotransmitter diffuses and flows through the extracellular space from its site of release and binds to extrasynaptic receptors at various distances from the source. Based on evidence from our laboratory the concept is introduced that neurotransmitters in the amygdala can modulate anxiety involving changes in fear learning and memories by effects on receptor mosaics in the fear circuits through wiring and volume transmission modes of communication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aggleton JP (ed) (2000) The amygdala: a functional analysis. University Press, Oxford

    Google Scholar 

  2. Shinnick-Gallagher P, Pitkänen A, Shekhar A, Cahill L (eds) (2003) The amygdala in brain function. Basic and clinical approaches. New York Academy of Sciences, New York

    Google Scholar 

  3. Le Doux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184

    CAS  Google Scholar 

  4. Davis M, Whalen PJ (2001) The amygdala: vigilance and emotion. Mol Psychiatr 6:13–34

    CAS  Google Scholar 

  5. Millan MJ (2003) The neurobiology and control of anxious states. Prog Neurobiol 70:83–244

    PubMed  CAS  Google Scholar 

  6. Paré D, Quirk G, LeDoux JE (2004) New vistas on amygdala networks in conditioned fear. J Neurophysiol 92:1–9

    PubMed  Google Scholar 

  7. Agnati LF, Fuxe K, Zoli M, Ozini I, Toffano G, Ferraguti F (1986) A correlation analysis of the regional distribution of central enkephalin and beta-endorphin immunoreactive terminals and of opiate receptors in adult and young male rats. Evidence for the existence of two main types of communication in the central nervous system: the volume transmission and the wiring transmission. Acta Physiol Scand 128:201–207

    PubMed  CAS  Google Scholar 

  8. Fuxe K, Dahlström A, Höistad M, Marcellino D, Jansson A, Rivera A, Diaz-Cabiale Z, Jacobsen K, Tinner-Staines B, Hagman B, Leo G, Staines G, Guidolin G, Kehr Genedani S, Belluardo N, Agnati LF (2007) From the Golgi-Cajal mapping to the transmitter-based characterization of the neural networks leading to two modes of brain communication: wiring an volume transmission. Brain Res Rev 55:17–54

    PubMed  CAS  Google Scholar 

  9. McDonald AJ (1998) Cortical pathways to the mammalian amygdala. Prog Neurobiol 55:257–332

    PubMed  CAS  Google Scholar 

  10. LeDoux JE, Ciccetti P, Xagoraris A, Romanski L-M (1990) The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning. J Neurosci 10:1062–1069

    PubMed  CAS  Google Scholar 

  11. Pitkänen A, Stefanacci L, Farb CR, Go G-G, Le Doux JE, Amaral DG (1995) Intrinsec connections of the rat amygdaloid complex: projections originating from the lateral nucleus. J Comp Neurol 356:288–310

    PubMed  Google Scholar 

  12. Hopkins DA, Holstege G (1978) Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat. Exp Brain Res 32:529–547

    PubMed  CAS  Google Scholar 

  13. Krettek JE, Price JL (1978) Amygdaloid projections to subcortical structures within the basal forebrain and brain stem in the rat and cat. J Comp Neurol 178:225–254

    PubMed  CAS  Google Scholar 

  14. Veeinig JG, Swanson LW, Sawchenko PE (1984) The organization of projections from the central nucleus of the amygdala to brain stem-sites involved in central autonomic regulation: a combined retrograde transport-immunohistochemical study. Brain Res 303:337–357

    Google Scholar 

  15. Cassell MD, Gray TS, Kiss JZ (1986) Neuronal architecture in the rat central nucleus of the amygdala. J Comp Neurol 246:478–499

    PubMed  CAS  Google Scholar 

  16. Gray TS (1989) Autonomic neuropeptide connections of the amygdala. In: Tache Y, Morley JE, Brown MR (eds) Neuropeptides and stress. Springer-Verlag, New York, pp 92–106

    Google Scholar 

  17. Sun N, Yi H, Cassell MD (1994) Evidence for a GABAergic interface between cortical afferents and brainstem projection neurons in the rat central extended amygdala. J Comp Neurol 340:43–64

    PubMed  CAS  Google Scholar 

  18. Royer S, Martina M, Paré D (1999) An inhibitory interface gates impulse traffic between the input and output stations of the amygdala. J Neurosci 19:10575–10583

    PubMed  CAS  Google Scholar 

  19. Royer S, Martina M, Paré D (2000) Polarized synaptic interactions between intercalated neurons of the amygdala. J Neurophysiol 83:3509–3518

    PubMed  CAS  Google Scholar 

  20. Scibilia RJ, Lachowicz JE, Kilts CD (1992) Topographic non overlapping distribution of D1 and D2 receptors in the amygdaloid nuclear complex of the rat brain. Synapse 11:146–154

    PubMed  CAS  Google Scholar 

  21. Fuxe K, Jacobsen KX, Höistad M, Tinner B, Jansson A, Staines WA, Agnati LF (2003) The dopamine D1 receptor-rich main and paracapsular intercalated nerve cell groups of the rat amygdala: relationships to the dopamine innervation. Neuroscience 119:733–746

    PubMed  CAS  Google Scholar 

  22. Nitecka L, Ben-Ari Y (1987) Distribution of GABA-like immunoreactivity in the rat amygdaloid complex. J Comp Neurol 266:45–55

    PubMed  CAS  Google Scholar 

  23. McDonald AJ, Augustine JR (1993) Localization of GABA-like immunoreactivity in the monkey amygdala. Neuroscience 52:281–294

    PubMed  CAS  Google Scholar 

  24. Paré D, Smith Y (1993) Distribution of GABA immunoreactivity in the amygdaloid complex of the cat. Neuroscience 57:1061–1076

    PubMed  Google Scholar 

  25. Millhouse OE (1986) The intercalated cells of the amygdala. J Comp Neurol 247:246–271

    PubMed  CAS  Google Scholar 

  26. Paré D, Smith Y (1993) The intercalated cell masses project to the central and medial nuclei of the amygdala in cats. Neuroscience 57:1077–1090

    PubMed  Google Scholar 

  27. Smith Y, Paré D (1994) Intra-amygdaloid projections of the lateral nucleus in the cat: PHA-L anterograde labelling combined with postembeding GABA and glutamate immunocytochemistry. J Comp Neurol 342:232–248

    PubMed  CAS  Google Scholar 

  28. Nose I, Higashi H, Inokuchi H, Nishi S (1991) Synaptic responses of guinea pig and rat central amygdala neurons in vitro. J Neurophysiol 65:1227–1247

    PubMed  CAS  Google Scholar 

  29. Alheid GF, de Olmos JS, Beltramino CA (1995) Amygdala and extended amygdala. In: Paxinos G (ed) The rat nervous system. Academic Press, San Diego, pp 495–578

    Google Scholar 

  30. Marowsky A, Yanagawa Y, Obata K, Vogt KE (2005) A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 48:1025–1037

    PubMed  CAS  Google Scholar 

  31. Rosenkranz JA, Grace AA (2002) Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo. J Neurosci 22:324–337

    PubMed  CAS  Google Scholar 

  32. Quirk JG, Likhtic E, Pelletier JG, Paré D (2003) Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci 23:8800–8807

    PubMed  CAS  Google Scholar 

  33. Likhtik E, Pelletier JG, Paz R, Paré D (2005) Prefrontal control of the amygdala. J Neurosci 25:7429–7437

    PubMed  CAS  Google Scholar 

  34. Sun N, Cassell MD (1993) Intrinsic GABAergic neurons in the rat central amygdala. J Comp Neurol 330:381–404

    PubMed  CAS  Google Scholar 

  35. Sullivan RM, Henke PG, Ray A, Herbert MA, Trimper JM (1989) The GABA/benzodiazepine receptor complex in the central amygdalar nucleus and stress ulcers in rats. J Comp Neurol 330:381–404

    Google Scholar 

  36. Saper CB (1982) Convergence of autonomic and limbic connections in the insular cortex of the rat. J Comp Neurol 210:163–173

    PubMed  CAS  Google Scholar 

  37. Yasui Y, Breder CD, Saper CB, Cechetto DF (1991) Autonomic responses and efferent pathways from the insular cortex in the rat. J Comp Neurol 303:355–374

    PubMed  CAS  Google Scholar 

  38. Miranda MI, Ferreira G, Ramírez-Lugo L, Fernández-Rattoni F (2002) Glutamatergic activity in the amigdala signals viceral input during taste memory formation. Proc Natl Acad Sci USA 99:11417–11422

    PubMed  CAS  Google Scholar 

  39. Swanson LW (1976) An autoradiographic study of the efferent connections of the preoptic region of the rat. J Comp Neurol 167:227–256

    PubMed  CAS  Google Scholar 

  40. Bernard JF, Carroue J, Besson JM (1991) Efferent projections from the external parabrachial area to the forebrain: a Phaseolus vulgaris leucoagglutinin study in the rat. Neurosci Lett 122:257–260

    PubMed  CAS  Google Scholar 

  41. Turner BH, Herkenham M (1991) Thalamo amygdaloid projections in the rat: a test of amygdala’s role in sensory processing. J Comp Neurol 313:295–325

    PubMed  CAS  Google Scholar 

  42. Burns LH, Everitt BJ, Robbins TW (1994) Intra-amygdaloid infusion on the N-Methyl-d-aspartate receptor antagonist AP5 impairs acquisition but not performance of discriminated approach to an appetitive CS. Behav Neural Biol 61:242–250

    PubMed  CAS  Google Scholar 

  43. Everitt BJ, Cardinal RN, Parkinson JA, Robbins TW (2003) Appetitive behavior. Impactof amygdala-dependent mechanisms of emotional learning. Ann NY Acad Sci 985:233–250

    PubMed  Google Scholar 

  44. McDonald AJ, Mascagni F, Guo L (1996) Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience 71:55–75

    PubMed  CAS  Google Scholar 

  45. Barreta S, Pantazopoulos H, Caldera M, Pantazopouls P, Paré D (2005) Infralimbic cortex activation increases c-fos expression in intercalated neurons of the amygdala. Neuroscience 132:943–953

    Google Scholar 

  46. Milad MR, Quirk GJ (2002) Neurons in the medial prefrontal cortex signal memory for fear extinction. Nature 420:70–74

    PubMed  CAS  Google Scholar 

  47. Wu LJ, Ko SW, Toyoda H, Zhao MG, Xu H, Vadakkan KI, Ren M, Knifed E, Shum F, Quan J, Zhang XH, Zhuo M (2007) Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice. PLoS ONE 2:e167

    PubMed  Google Scholar 

  48. Nicholls JG, Martin AR, Wallace BC (1992) From neuron to brain. A cellular and molecular approach to the function of the nervous system. Sinauer Associates, Massachusets, pp 184–338

    Google Scholar 

  49. Greengard P (2001) The neurobiology of dopamine signalling. Biosci Rep 21:247–69

    PubMed  CAS  Google Scholar 

  50. Hökfelt T, Rehfeld JF, Skirboll L, Ivemark B, Goldstein M, Markey K (1980) Evidence for coexistence of dopamine and CCK in meso-limbic neurons. Nature 285:476–478

    PubMed  Google Scholar 

  51. Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7:867–879

    PubMed  Google Scholar 

  52. Ghijsen WE, Leenders AG, Wiegant VM (2001) Regulation of cholecistokinin release from central nerve terminals. Peptides 22:1213–1221

    PubMed  CAS  Google Scholar 

  53. Rotzinger S, Vaccarino FJ (2003) Cholecystokinin receptor subtypes: role in the modulation of anxiety-related and reward-related behaviours in animal models. J Psychiatr Neurosci 28:171–181

    Google Scholar 

  54. Greengard P, Nairn AC, Girault JA, Ouimet CC, Snyder GL, Fisone G, Allen PB, Fienberg A, Nishi A (1998) The DARPP-32/protein phosphatase-1 cascade: a model for signal integration. Brain Res Rev 26:274–84

    PubMed  CAS  Google Scholar 

  55. Kandell ER (1997) Genes, synapses and long-term memory. J Cell Physiol 173:124–125

    Google Scholar 

  56. Agnati LF, Ferre S, Lluis C, Franco R, Fuxe K (2003) Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among hepthelical receptors with examples from the striatopallidal GABA neurons. Pharmacol Rev 55:509–550

    PubMed  CAS  Google Scholar 

  57. Fuxe K, Canals M, Torvinen M, Marcellino D, Terasmaa A, Genedani S, Leo G, Guidolin D, Diaz-Cabiale Z, Rivera A, Lundstrom L, Langel U, Narváez J, Tanganelli S, Lluis C, Ferre S, Woods A, Franco R, Agnati LF (2007) Intramembrane receptor-receptor interactions: a novel principle in molecular medicine. J Neural Transm 114:49–75

    PubMed  CAS  Google Scholar 

  58. Fuxe K, Marcellino D, Rivera A, Diaz-Cabiale Z, Filip M, Gago B, Roberts DCS, Langel U, Genedani S, Ferraro L, de la Calle A, Narvaez J, Tanganelli S, Woods A, Agnati LF (2008) Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology. Brain Res Rev [Epub ahead of print]

  59. Kuhar MJ, Unnerstall JR, De Souza EB (1985) Receptor mapping in neuropharmacology by autoradiography: some technical problems. NIDA Res Monogr 62:1–12

    PubMed  CAS  Google Scholar 

  60. Mundorf ML, Joseph JD, Austin CM, Caron MG, Wightman RM (2001) Catecholamine release and uptake in the mouse prefrontal cortex. J Neurochem 79:130–142

    PubMed  CAS  Google Scholar 

  61. Miles PR, Mundorf ML, Whightman MR (2002) Release and uptake of catecholamines in the bed nucleus of the stria terminalis measured in the mouse brain slice. Synapse 44:188–197

    PubMed  CAS  Google Scholar 

  62. Zhu PC, Thureson-Klein Å, Klein RL (1986) Exocytosis from large cored vesicles outside the active synaptic zones of terminals within the trigeminal subnucleus caudalis: a possible mechanism for neuropeptide release. Neuroscience 19:43–54

    PubMed  CAS  Google Scholar 

  63. Thureson-Klein ÅK, Klein RL (1990) Exocytosis from neuronal large dense-cored vesicles. Int Rev Cytol 121:77–126

    Google Scholar 

  64. Descarries L, Watkins KC, Lapierre Y (1977) Noradrenergic axon terminals in the cerebral cortex of rat. III. Topometric structural analysis. Brain Res 133:197–222

    PubMed  CAS  Google Scholar 

  65. Descarries L, Watkins KC, Garcia S, Bosler O, Doucet G (1996) Dual character, asynaptic and synaptic of dopamine innervation in adult rat striatum: a quantitative autoradiographic and immunohistochemical analysis. J Comp Neurol 375:167–186

    PubMed  CAS  Google Scholar 

  66. Descarries L, Mechawar N (2000) Ultrastructural evidence for diffuse transmission by monoamine and acetylcholine neurons of the central nervous system. Prog Brain Res 125:27–47

    PubMed  CAS  Google Scholar 

  67. Szapiro G, Barbour B (2007) Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover. Nature Neurosci 10:735–742

    PubMed  CAS  Google Scholar 

  68. Smith SL, Otis TS (2005) Pattern–dependent, simultaneous plasticity differentially transforms the input–output relationship of a feedforward circuit. Proc Natl Acad Sci USA 102:14901–14906

    PubMed  CAS  Google Scholar 

  69. Agnati LF, Guidolin G, Leo G, Fuxe K (2007) A Boolean network modeling of receptor mosaics relevance of topology and cooperativity. J Neural Transm 114:77–92

    PubMed  CAS  Google Scholar 

  70. Guidolin D, Fuxe K, Neri G, Nussdorfer GG, Agnati LF (2007) On the role of receptor-receptor interactions and volume transmission in learning and memory. Brain Res Rev 55:119–133

    PubMed  Google Scholar 

  71. Agnati LF, Franzén O, Ferré S, Leo G, Franco R, Fuxe K (2003) Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus of motor learning in the basal ganglia. J Neural Transm Suppl 65:1–28

    PubMed  Google Scholar 

  72. Fuxe K, Agnati LF (1991) Two principal modes of electrochemical communication in the brain: volume versus wiring transmission. In: Fuxe K, Agnati LF (eds) Volume Transmission in the brain: novel mechanisms for neural transmission. Raven Press, New York, pp 1–9

    Google Scholar 

  73. Agnati LF, Fuxe K (2000) Volume transmission as a key feature of information handling in the central nervous system possible new interpretative value of the Turing’s B-type machine. Prog Brain Res 125:3–19

    Article  PubMed  CAS  Google Scholar 

  74. Jansson A, Descarries L, Cornea-Hebert V, Riad M, Verge D, Bancila M, Agnati LF, Fuxe K (2002) Transmitter-receptor mismatches in central dopamine, serotonin and neuropeptide systems. In: Walz W (ed) The neuronal environment: brain homeostasis in health and disease. Humana Press, Totowa, NJ, pp 83–107

    Google Scholar 

  75. Fuxe K, Rivera A, Jacobsen KX, Hoistad M, Leo Horvath TL, Staines W, de la Calle A (2005) Dynamics of volume transmission in the brain. Focus on catecholamine and opiod peptide communication and the role of uncoupling protein 2. J Neural Transm 112:65–76

    PubMed  CAS  Google Scholar 

  76. Agnati LF, Leo G, Zanardi A, Genedani S, Rivera A, Fuxe K, Guidolin D (2006) Volume transmission and wiring transmission from cellular to molecular networks: History and perspectives. Acta Physiol (Oxford) 187:329–344

    CAS  Google Scholar 

  77. Nicholson C, Syková E (1998) Extracellular space structure revealed by diffusion analysis. Trends Neurosci 21:207–215

    PubMed  CAS  Google Scholar 

  78. Zoli M, Jansson A, Syková E, Agnati LF, Fuxe K (1999) Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol Sci 20:142–150

    PubMed  CAS  Google Scholar 

  79. Cragg SJ, Rice ME (2004) Dancing past the DAT at a DA synapse. Trends Neurosci 27:270–277

    PubMed  CAS  Google Scholar 

  80. Duggan AW, Hope PJ, Jarrot B, Schaible HG, Fleetwood-Walker SM (1990) Release, spread and persistence of immunoreactive neurokinin A in the dorsal horn of the cat following noxious cutaneous stimulation. Studies with antibody microprobes. Neuroscience 35:195–202

    PubMed  CAS  Google Scholar 

  81. Duggan AW, Schaible HG, Hope PJ, Lang CW (1992) Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes. Brain Res 579:261–269

    PubMed  CAS  Google Scholar 

  82. De Wied D, Jolles J (1982) Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects. Physiol Rev 62:976–1059

    PubMed  Google Scholar 

  83. Davis TP, Konings PN (1993) Peptidases in the CNS: formation of biologically active, receptor-specific peptide fragments. Crit Rev Neurobiol 7:163–174

    PubMed  CAS  Google Scholar 

  84. Pérez de la Mora M, Lara-García D, Jacobsen KX, Vásquez-García M, Crespo-Ramírez M, Flores-Gracia C, Escamilla-Marvan E, Fuxe K (2006) Anxyolytic-like effects of the selective metabotropic glutamate receptor 5 antagonist MPEP after its intra-amygdaloid microinjection in three different non-conditioned rat models of anxiety. Eur J Neurosci 23:2749–2759

    PubMed  Google Scholar 

  85. Van Dijk A, Richards JG, Trzeciak A, Gillesen D, Möhler H (1984) Cholecystokinin receptors: biochemical demonstration and autoradiographical localization in the rat brain and pancreas using (3H) cholecystokinin8 as radioligand. J Neurosci 4:1021–1033

    PubMed  Google Scholar 

  86. Hill DR, Campbell NJ, Shaw TM, Woodruff GN (1987) Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in the rat CNS using highly selective nonpeptide CCK antagonist. J Neurosci 7:2967–2976

    PubMed  CAS  Google Scholar 

  87. Morency MA, Quirion R, Mishra RK (1994) Distribution of cholecystokinin receptors in the bovine brain. A quantitative autoradiographic study. Neuroscience 62:307–316

    PubMed  CAS  Google Scholar 

  88. Wank SA, Pisegna JR, de Weerth A (1994) Cholecystokinin receptor family. Molecular cloning, structure, and functional expression in the rat, guinea pig, and human. Ann NY Acad Sci 713:49–66

    PubMed  CAS  Google Scholar 

  89. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Meth 14:149–167

    CAS  Google Scholar 

  90. Pérez de la Mora M, Hernández-Gómez AM, Arizmendi-García Y, Jacobsen K, Lara-García D, Flores-Gracia C, Crespo-Ramírez M, Gallegos-Cari A, Nuche-Bricaire A, Fuxe K (2007) Role of the amygdaloid cholecystokinin (CCK/gastrin)-2 receptors and terminal networks in the modulation of anxiety-like behavior and [3H]GABA release. Eur J Neurosci 26:3614–3630

  91. Treit D, Menard J, Pesold C (1994) The shock-probe/burying test. Neurosci Protoc 94-010-02-01–94-010-02-09

  92. Fernández-Guasti A, Ferreira A, Picazo O (2001) Diazepam but not buspirone induces similar anxiolytic-like effects in lactating and ovariectomized Wistar rats. Pharmacol Biochem Behav 70:85–93

    PubMed  Google Scholar 

  93. Costall B, Jones BJ, Kelly ME, Naylor RJ, Tomkins DM (1989) Exploration of mice in a black and white test box: validation as a model of anxiety. Pharmacol Biochem Behav 32:777–785

    PubMed  CAS  Google Scholar 

  94. Pérez de la Mora M, Cárdenas-Cachon L, Vázquez-García M, Crespo-Ramírez M, Jacobsen K, Höisted M, Agnati L, Fuxe K (2005) Anxiolytic effects of intra-amygdaloid injection of the D1 antagonist SCH23390 in the rat. Neurosci Lett 377:101–105

    Google Scholar 

  95. Killcross S, Robins TW, Everitt BJ (1997) Different types of fear-conditioned behaviour mediated by separate nuclei within the amygdala. Nature 388:377–380

    PubMed  CAS  Google Scholar 

  96. Broekkamp CLE, Berendsen HHG, Jenck F, Van Delft AM (1989) Animal models for anxiety and response to serotonergic drugs. Psychopathology 22(Suppl 1):2–12

    Article  PubMed  Google Scholar 

  97. Harro J, Vasar E (1991) Evidence that CCKB receptors mediate the regulation of exploratory behaviour in the rat. Eur J Pharmacol 193:379–381

    PubMed  CAS  Google Scholar 

  98. Chopin Ph, Briley M (1993) The benzodiazepine antagonist flumazenil blocks the effects of CCK receptor agonists and antagonists in the elevated plus-maze. Psychopharmacology 110:409–414

    Google Scholar 

  99. Rex A, Barth T, Voight J-P, Domeny AM, Fink H (1994) Effects of cholecystokinin tetrapeptide and sulphated cholecystokinin octapeptide in rat models of anxiety. Neurosci Lett 172:139–142

    PubMed  CAS  Google Scholar 

  100. van Megen HJGM, Westenberg HGM, den Boer JA, Kahn RS (1996) Cholecystokinin in anxiety. Eur Neuropsychopharmacol 6:263–280

    PubMed  Google Scholar 

  101. Wang H, Wong PT, Spiess J, Zhu YZ (2005) Cholecystokinin-2 (CCK2) receptor-mediated anxiety-like behaviors in rats. Neurosci Biobehav Rev 29:1361–1373

    PubMed  CAS  Google Scholar 

  102. Hernández-Gómez AM, Aguilar-Roblero R, Pérez de la Mora M (2002) Role of cholecystokinin-A and cholecystokinin-B receptors in anxiety. Amino Acids 23:283–290

    PubMed  Google Scholar 

  103. Frankland PW, Josselyn SA, Bradwejn J, Vaccarino FJ, Yeomans JS (1997) Activation of amygdala cholecystokinin B receptors potentiates the acoustic startle response in the rat. J Neurosci 17:1838–1847

    PubMed  CAS  Google Scholar 

  104. Rodrigues SM, Bauer EP, Farb CR, Le SchafeGE, Doux JE (2002) The group I metabotropic glutamate receptor mGluR5 is required for fear memory formation and long term potentiation in the lateral amygdala. J Neurosci 22:5219–5229

    PubMed  CAS  Google Scholar 

  105. Fendt M, Schmid S (2002) Metabotropic glutamate receptors are involved in amygdaloid plasticity. Eur J Neurosci 15:1535–1541

    PubMed  Google Scholar 

  106. Lamont EW, Kokkinidis L (1998) Infusión of the dopamine D1 receptor antagonist SCH23390 into the amygdala blocks fear expresión in a potentiated startle paradigm. Brain Res 795:128–136

    PubMed  CAS  Google Scholar 

  107. Guarraci FA, Frohardt RJ, Kapp BS (1999) Amygdaloid dopamine D1 receptor involvement in Pavlovian fear conditioning. Brain Res 827:28–40

    PubMed  CAS  Google Scholar 

  108. Nelolkov A, Areda T, Innos J, Koks S, Vasar E (2006) Rats displaying distinct exploratory activity also have different expression patterns of gamma-aminobutyric acid- and cholecystokinin-related genes in brain regions. Brain Res 1100:21–31

    Google Scholar 

  109. Tsutsumi T, Akiyoshi J, Hikichi T, Kiyota A, Kohono Y, Katsuragi S, Yamamoto Y, Isogawa K, Nagayama H (2001) Suppression of conditioned fear by the administration of CCK-B receptor antisense oligodeoxynucleotide into the lateral ventricle. Pharmacopsychiatry 34:232–237

    PubMed  CAS  Google Scholar 

  110. Cohen H, Kaplan Z, Kotler M (1998) Inhibition of anxiety in rats by antisense to cholecystokinin precursor protein. Biol Psychiatry 44:915–917

    PubMed  CAS  Google Scholar 

  111. Pratt JA, Brett RR (1995) The benzodiazepine receptor inverse agonist FG 7142 induces cholecystokinin gene expression in rat brain. Neurosci Lett 184:197–200

    PubMed  CAS  Google Scholar 

  112. Hebb AL, Zacharko RM, Dominguez H, Laforest S, Gauthier M, Levac C, Drolet G (2003) Changes in brain cholecystokinin and anxiety-like behavior following exposure to mice to predator odor. Neuroscience 116:539–551

    PubMed  CAS  Google Scholar 

  113. Giardino L, Bettelli C, Pozza M, Calzá L (1999) Regulation of CCK mRNA expression in the rat brain by stress and treatment with setraline, a selective serotonin re-uptake inhibitor. Brain Res 824:304–307

    PubMed  CAS  Google Scholar 

  114. Chen Q, Nakajima A, Meacham C, Tang Y-P (2006) Elevated cholecystokinergic tone constitutes an important molecular/neuronal mechanism for the expression of anxiety in the mouse. Proc Natl Acad Sci USA 103:3881–3886

    PubMed  CAS  Google Scholar 

  115. Li Q, Deng X, Singh P (2007) Significant increase in the aggressive behavior of transgenic mice overexpressing peripheral prograstin peptides: associated changes in CCK-2 and serotonin receptors in the CNS. Neuropsychopharmacology 32:1813–1821

    PubMed  CAS  Google Scholar 

  116. Raud S, Rünkorg K, Veraksitš A, Reimets A, Nelovokov A, Abramov U, Matsui T, Bourin M, Volke V, Koks S, Vasar E (2003) Targeted mutation of CCK2 receptor gene modifies the behavioural effects of diazepam in female mice. Psychopharmacology 168:417–425

    PubMed  CAS  Google Scholar 

  117. Horinouchi Y, Akiyoshi J, Nagata A, Matsushita H, Tsutsumi T, Isogawa K, Noda T, Nagayama H (2004) Reduced anxious behavior in mice lacking the CCK-2 receptor gene. Eur Neuropsychopharmacol 14:157–161

    PubMed  CAS  Google Scholar 

  118. Daugé V, Sebret A, Beslot F, Matsui T, Roques BP (2001) Behavioral profile of CCK2 receptor-deficient mice. Neuropsychopharmacology 25:690–698

    PubMed  Google Scholar 

  119. Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, Matsui T, Noda T, Takiguchi S, Takata Y, Kawanami T, Funakoshi A (2002) Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor knockout mice in the plus-maze. Neurosci Lett 335:115–118

    PubMed  CAS  Google Scholar 

  120. Spooren WPJM, Vasout A, Neijt HC, Kuhn R, Gasparini F, Roux S, Porsolt RD, Gentsch C (2000) Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethy) piridine in rodents. J Pharmacol Exp Ther 295:1267–1275

    PubMed  CAS  Google Scholar 

  121. Tatarcynska E, Klodzinska A, Chojnacka-Wojcik E, Palucha A, Ga F, Kuhn R, Pilc A (2001) Potential anxiolytic- and antidepressant-like effects of MPEP a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 132:1423–1430

    Google Scholar 

  122. Brodkin J, Bradbury M, Busse C, Warren M, Bristow MJ, Varney MA (2002) Reduced stress-induced hyperthermia in mGluR5 knockout mice. Eur J Neurosci 16:2241–2244

    PubMed  CAS  Google Scholar 

  123. Simon O, Panissaud C, Constentin J (1992) Sulpiride anxiogenic-like effect inhibition by a D1 dopamine receptor antagonist. NeuroReport 3:941–942

    PubMed  CAS  Google Scholar 

  124. Pogorelov VM, Rodriguiz RM, Caron MG, Insco ML, Wetsel WC (2005) Novelity seeking and stereotypic activation of behavior in mice with disruption of the Dat I gene. Neuropsychopharmacology 30:1818–1831

    PubMed  CAS  Google Scholar 

  125. Drago J, Gerfen CR, Lachowitz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP, Bartlett PF, Jose PA, Sibely DR, Westphal H (1994) Altered striatal function in a mutant mice lacking D1A dopamine receptors. Proc Nat Acad Sci USA 91:12564–12568

    PubMed  CAS  Google Scholar 

  126. Karasinska JA, George SR, El-Guhndi M, Fletcher PJ, O’Dowd BF (2000) Modification of D1 receptor knockout phenotype in mice lacking both dopamine D1 and D3 receptors. Eur J Pharmacol 399:171–181

    PubMed  CAS  Google Scholar 

  127. Short JL, Ledent C, Drago J, Lawrence AJ (2006) Receptor crosstalk: characterization of mice deficient in dopamine D1 and adenosine2A receptors. Neuropsychopharmacology 31:525–534

    PubMed  CAS  Google Scholar 

  128. Steiner H, Fuchs S, Accili D (1997) D3 dopamine receptor-deficient mice: evidence for reduced anxiety. Physiol Behav 63:137–141

    PubMed  CAS  Google Scholar 

  129. El-Ghundi M, O’Dowd BF, George SR (2001) Prolonged fear responses in mice lacking dopamine D1 receptor. Brain Res 892:86–93

    PubMed  CAS  Google Scholar 

  130. Jaber M, Dumartin B, Sagné C, Haycock JW, Roubert C, Giros B, Bloch B, Caron MG (1999) Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter. Eur J Neurosci 11:3499–3455

    PubMed  CAS  Google Scholar 

  131. Drago J, Padungchaichot P, Accili D, Fuchs S (1998) Dopamine receptors and dopamine transporter in brain function and addictive behaviors: insights from targeted mouse mutants. Dev Neurosci 20:188–2003

    PubMed  CAS  Google Scholar 

  132. Wong JYF, Clifford JJ, Massals JS, Finkelstein DI, Horne MK, Waddington JL, Drago J (2003) Neurochemical changes in dopamine D1, D3, and D1/D3 receptor knockout mice. Eur J Pharmacol 472:39–47

    PubMed  CAS  Google Scholar 

  133. Marcellino D, Roberts DC, Navarro G, Filip M, Agnati L, Lluis C, Franco R, Fuxe K (2007) Increase in A2A receptors in the nucleus accumbens after extended cocaine self-administration and its disappearance after cocaine withdrawal. Brain Res 1143:208–220

    PubMed  CAS  Google Scholar 

  134. Linden AM, Bergeron M, Schoepp DD (2005) Comparison of c-fos induction in the brain by the mGlu2/3 receptor antagonist LY341495 and agonist LY354740. evidence for widespread endogenous tone at brain mGlu2/3 receptors in vivo. Neuropharmacology 49(Suppl 1):120–134

    PubMed  CAS  Google Scholar 

  135. Shigemoto R, Nomura S, Ohishi H, Suhihara H, Nakanishi S, Mizuno N (1993) Immunohistochemical localization of a metabotropic glutamate receptor, mgluR5 in the rat brain. Neurosci Lett 163:53–57

    PubMed  CAS  Google Scholar 

  136. Romano C, Sesma NA, McDonald CT, O’Malley K, van den Pol AN, Olney JW (1995) J Comp Neurol 355:455–469

    PubMed  CAS  Google Scholar 

  137. Wieronska JM, Smialowska M, Branski M, Gasparini F, Klodzinska A, Szewczyk B, Palucha A, Chojnacka-Wojcik E, Pilk A (2004) In the amygdala anxiolytic action of mGluR5 receptor antagonist MPEP involves neuropeptide Y but not GABA signalling. Neuropsychopharmacology 29:514–521

    PubMed  CAS  Google Scholar 

  138. Farb C, Aoki C, Milner T, Kaneko T, LeDoux J (1992) Glutamate immunoreactive terminals in the lateral amygdaloid nucleus: a possible substrate for emotional memory. Brain Res 593:145–158

    PubMed  CAS  Google Scholar 

  139. Kim M, Campeau S, Falls WA, Davis M (1993) Infusion of the non-NMDA receptor antagonist CNQX into the amygdala blocks the expression of fear potentiated startle. Behav Neural Biol 59:5–8

    PubMed  CAS  Google Scholar 

  140. Sajdyk TJ, Shekhar A (1997) Excitatory amino acid receptors in the basolatewral amygdala regulate anxiety responses in the social interaction test. Brain Res 764:262–264

    PubMed  CAS  Google Scholar 

  141. Rosenkranz JA, Grace AA (1999) Modulation of basolateral amygdala neuronal firing and afferent drive by dopamine receptor activation in vivo. J Neurosci 19:11027–11039

    PubMed  CAS  Google Scholar 

  142. McGrath J, Campbell KM, Veldman MB, Burton FH (1999) Anxiety in a transgenic mouse model of cortico-limbic neuropotentiated compulsive behavior. Behav Pharmacol 10:435–443

    Article  PubMed  CAS  Google Scholar 

  143. Zarbin NA, Innis NB, Wamsley JK, Snyder SH, Kuhar MJ (1983) Autoradiographic localization of cholecystokinin in rodent brain. J Neurosci 3:877–906

    PubMed  CAS  Google Scholar 

  144. Pelaprat D, Broer Y, Studler JM, Peschanski M, Tassin JP, Glowinski J, Rostene W, Roques BP (1987) Autoradiography of CCK receptors in the rat brain using [3H]Boc [NLE28, 31]CCK27–33 and [125I]Bolton-Hunter CCK8. Functional significance of subregional distribution. Neurochem Int 10:495–508

    CAS  PubMed  Google Scholar 

  145. Honda T, Wada E, Battey JF, Wank SA (1993) Differential expression of CCKa and CCKb receptors in the rat brain. Mol Cell Neurosci 4:143–154

    CAS  PubMed  Google Scholar 

  146. Mercer LD, Le VQ, Nunan J, Jones MN, Beart PM (2000) Direct visualization of cholecystokinin subtype2 receptors in the rat central nervous system using anti-peptides antibodies. Neurosci Lett 293:167–170

    PubMed  CAS  Google Scholar 

  147. Fendt M, Fanselow MS (1999) The neuroanatomical and neurochemical basis of conditioned fear. Biobehav Rev 23:743–760

    CAS  Google Scholar 

  148. Vyas A, Pillai AG, Chattarji S (2004) Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience 128:667–673

    PubMed  CAS  Google Scholar 

  149. Conn PJ, Battaglia G, Marino MJ, Nicoletti F (2005) Metabotropic glutamate receptors in the basal ganglia motor circuit. Nat Rev Neurosci 6:787–798

    PubMed  CAS  Google Scholar 

  150. Ferré S, Agnati LF, Ciruela F, Lluis G, Woods AS, Fuxe K, Franco R (2007) Neurotransmitter receptor heteromers and their integrative role in “local modules”. Their striatal spine module. Brain Res Rev 55:55–67

    PubMed  Google Scholar 

  151. Balschun D, Wetzel W (2002) Inhibition of mGluR5 blocks hippocampal LTP in vivo and special learning in rats. Pharmacol Biochem Behav 73:375–380

    PubMed  CAS  Google Scholar 

  152. Alagarsamy S, Sorensen SD, Cohnn PJ (2001) Coordinate regulation of metabotropic glutamate receptors. Curr Opin Neurobiol 11:357–362

    PubMed  CAS  Google Scholar 

  153. Pisani A, Gubellini P, Bonsi P, Conquet F, Picconi B, Centonze D, Bernardi G, Calabresi P (2001) Metabotropic glutamate receptor 5 mediates potentiation of N-methyl-d-aspartate responses in medium spiny striatal neurons. Neuroscience 106:579–587

    PubMed  CAS  Google Scholar 

  154. De Blasi A, Conn PJ, Pin J, Nicoletti F (2001) Molecular determinants of metabotropic glutamate signaling. Trends Pharmacol Sci 22:114–120

    PubMed  Google Scholar 

  155. Lu YM, Jia Z, Janus C, Henderson JT, Gerlai R, Wojtowicz JM, Roder JC (1997) Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long term potentiation (LTP) but normal CA3 LTP. J Neurosci 17:5196–5205

    PubMed  CAS  Google Scholar 

  156. Jia Z, Lu Y, Henderson J, Taverna F, Romano C, Abramow-Newerly W, Wojtowicz JM, Roder JC (1997) Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5. Learn Mem 5:331–343

    Google Scholar 

  157. Ehlers MD (1999) Synapse structure:glutamate receptors connected by the shanks. Curr Biol 9:R848–R850

    PubMed  CAS  Google Scholar 

  158. Naisbitt S, Kim E, Cheng Tu J, Xiao B, Sala C, Valtschanoff J, Weimberg LJ, Worley PF, Sheng M (1999) Shank, a novel family of postsynaptic density proteins that binds to NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23:569–582

    PubMed  CAS  Google Scholar 

  159. Inglis FM, Moghaddam B (1999) Dopaminergic innervations of the amygdala is highly responsive to stress. J Neurochem 72:1088–1094

    PubMed  CAS  Google Scholar 

  160. El-Ghundi M, Fletcher PJ, Drago J, Sibley DR, O’Dowd BF, George SR (1999) Spatial learning deficit in dopamine D1 receptor knockout mice. Eur J Pharmacol 383:95–106

    PubMed  CAS  Google Scholar 

  161. Levine MS, Altemus KL, Cepeda C, Cromwell HC, Crawford C, Ariano MA, Drago J, Sibley DR, Westphal H (1996) Modulatory actions of dopamine on NMDA–receptor mediated responses are reduced in D (1A)-deficient mutant mice. J Neurosci 16:5870–5882

    PubMed  CAS  Google Scholar 

  162. Lee FJ, Xue S, Pei L, Vukusic B, Chery N, Wang Y, Wang YT, Niznik HB, Yu XM, Liu F (2002) Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell 111:219–230

    PubMed  CAS  Google Scholar 

  163. Adamec R (1997) Transmitter systems involved in neural plasticity underlying increased anxiety and defence-Implications for understanding anxiety following traumatic stress. Neurosci Biobehav Rev 21:755–765

    PubMed  CAS  Google Scholar 

  164. File SE, Mabbutt PS, Hitchcott PK (1990) Characterisation of the phenomenon of “one-trial tolerance” to the anxiolytic effect of chlordiazepoxide in the elevated plus-maze. Psychopharmacology (Berl) 102:98–101

    CAS  Google Scholar 

  165. Fanselow MS, Gale GD (2003) The amygdala, fear, and memory. Ann NY Acad Sci 985:125–134

    PubMed  Google Scholar 

  166. Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–470

    PubMed  CAS  Google Scholar 

  167. Robinson ESJ, Nutt DJ, Jackson HC, Hudson AL (1997) Reviews: antisense oligonucleotides in psychopharmacology and behavior: promises and pitfalls. J Psychopharmacol 11:259–269

    PubMed  CAS  Google Scholar 

  168. Cryan JF, Thakker DR, Hoyer D (2007) Emerging use of non-viral RNA interference in the brain. Biochem Soc Trans 35:411–415

    PubMed  CAS  Google Scholar 

  169. Gingrich J, Roder JC (1998) Inducible gene expression in the nervous system of transgenic mice. Annu Rev Neurosci 21:377–405

    PubMed  CAS  Google Scholar 

  170. Mayford M, Kandel ER (1999) Genetic approaches to memory storage. Trends Genet 15:463–470

    PubMed  CAS  Google Scholar 

  171. Schultz W (2002) Getting formal with dopamine and reward. Neuron 36:241–263

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grant IN200508 from Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (UNAM) and by a grant from Swedish Research Council (04X-715).

Author information

Authors and Affiliations

  1. Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-253, Mexico, DF, 04510, Mexico

    Miguel Pérez de la Mora, Minerva Crespo-Ramírez & Candy Flores-Gracia

  2. Department of Cellular and Molecular Medicine, Neuroscience Research Institute, Ottawa, Canada

    Kirsten X. Jacobsen

  3. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Kjell Fuxe

Authors
  1. Miguel Pérez de la Mora
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kirsten X. Jacobsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minerva Crespo-Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Candy Flores-Gracia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kjell Fuxe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miguel Pérez de la Mora.

Additional information

Special issue article in honor of Dr. Ricardo Tapia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pérez de la Mora, M., Jacobsen, K.X., Crespo-Ramírez, M. et al. Wiring and Volume Transmission in Rat Amygdala. Implications for Fear and Anxiety. Neurochem Res 33, 1618–1633 (2008). https://doi.org/10.1007/s11064-008-9722-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-008-9722-9

Keywords

Search

Navigation