Skip to main content
SpringerLink
Log in

Effects of acute ethanol on corticotropin-releasing hormone and β-endorphin systems at the level of the rat central amygdala

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

The endogenous opioid and corticotropin-releasing hormone (CRH) systems, present in the central amygdala (CeA), are implicated in alcohol consumption.

Objectives

The purpose of this study is to investigate the hypothesis that, in CeA, alcohol stimulates CRH release, which then stimulates β-endorphin release.

Materials and methods

Rats were unilaterally implanted with a guide cannula to aim microdialysis probes in CeA. Experiment 1: rats received an intraperitoneal (IP) injection of various ethanol doses (0.0, 2.0, 2.4, or 2.8 g ethanol/kg body weight) and microdialysates were sampled at 30-min intervals to determine the effects over time of acute alcohol on the extracellular CRH concentrations in CeA. Experiment 2: phosphate-buffered saline, CRH, or CRH receptor (CRHR) antagonists (antalarmin or anti-sauvagine-30) was microinjected into CeA followed by a saline or 2.8 g/kg ethanol IP injection to determine the effects of CRHR activation or blockade in CeA on the basal and alcohol-stimulated release of β-endorphin. CRH and β-endorphin dialysate contents were determined using specific radioimmunoassays.

Results

Acute alcohol induced a delayed increase in the extracellular CRH levels in CeA. Behavioural data showed no difference in locomotion between alcohol- and saline-treated rats. However, a transient increase in grooming was observed which did not correspond with alcohol-induced changes in CRH. Local CRH microinjections increased the extracellular β-endorphin concentrations in CeA. CRHR1 and CRHR2 blockade with microinjections of antalarmin and anti-sauvagine-30, respectively, attenuated the alcohol-induced increase of extracellular β-endorphin in CeA.

Conclusions

Acute alcohol exerts indirect actions on CRH release and induced interactions of the CRH and β-endorphin systems in CeA.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

3V:

3rd ventricle

ANOVA:

Analysis of variance

ACTH:

Adrenocorticotropin hormone

BLA:

Basolateral amygdala

BSA:

Bovine serum albumin

BSTIA:

Bed nucleus of the stria terminalis intra-amygdaloid division

CA3:

Field CA3 of hippocampus

CeA:

Central amygdala

CPU:

Caudate putamen

CRH:

Corticotropin-releasing hormone

CRHR:

Corticotropin-releasing hormone receptors

CRHR1:

Corticotropin-releasing hormone receptors type 1

CRHR2:

Corticotropin-releasing hormone receptors type 2

DG:

Dentate gyrus

INJ:

Injection

IP:

Intraperitoneal

LH:

Lateral hypothalamus

MicroINJ:

Microinjection

PBS:

Phosphate-buffered saline

PIR:

Piriform cortex

RIA:

Radioimmunoassay

References

  • Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by naltrexone. Life Sci 26:679–688

    Article  PubMed  CAS  Google Scholar 

  • Bert L, Favale D, Jego G, Greve P, Guilloux J-P, Guiard BP, Gardier AM, Suaud-Chagny MF, Lestage P (2004) Rapid and precise method to locate microdialysis probe implantation in the rodent brain. J Neurosci Methods 140:53–57

    Article  PubMed  CAS  Google Scholar 

  • Bradbury AF, Smyth DG, Snell CR (1976) C fragment of lipotropin has a high affinity for brain opiate receptors. Nature 260:793–795

    Article  CAS  Google Scholar 

  • Buckingham JC (1986) Stimulation and inhibition of corticotrophin releasing factor secretion by beta endorphin. Neuroendocrinology 42:148–152

    Article  PubMed  CAS  Google Scholar 

  • Buckingham JC, Cooper TA (1986) Pharmacological characterization of opioid receptors influencing the secretion of corticotrophin releasing factor in the rat. Neuroendocrinology 44:36–40

    Article  PubMed  CAS  Google Scholar 

  • Chalmers DT, Lovenberg TW, De Souza EB (1995) Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. J Neurosci 15:6340–6350

    PubMed  CAS  Google Scholar 

  • Chang JK, Chang KJ (1983) The role of amino-terminal sequence of beta-endorphin and dynorphin in the determination of opiate receptor type selectivity. Life Sci 33:267–269

    Article  PubMed  CAS  Google Scholar 

  • Charmandari E, Constantine T, Chrousos G (2005) Endocrinology of the stress response. Annu Rev Physiol 67:259–284

    Article  PubMed  CAS  Google Scholar 

  • Cowen MS, Chen F, Lawrence AJ (2004) Neuropeptides: implications for alcoholism. J Neurochem 89:273–285

    Article  PubMed  CAS  Google Scholar 

  • Criado JR, Morales M (2000) Acute ethanol induction of c-Fos immunoreactivity in pre-pro-enkephalin expressing neurons of the central nucleus of the amygdala. Brain Res 861:173–177

    Article  PubMed  CAS  Google Scholar 

  • de Waele JP, Gianoulakis C (1993) Effects of single and repeated exposures of ethanol on hypothalamic beta-endorphin and CRH release by the C57BL/6 and DBA/2 strains of mice. Neuroendocrinology 57:700–709

    Article  PubMed  Google Scholar 

  • Froehlich JC, Harts J, Lumeng L, Li TK (1990) Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference. Pharmacol Biochem Behav 35:385–390

    Article  PubMed  CAS  Google Scholar 

  • Funk CK, O’Dell LE, Crawford EF, Koob GF (2006) Corticotrophin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci 26:11324–11332

    Article  PubMed  CAS  Google Scholar 

  • Garzon J, Sanchez-Blazquez P, Hollt V, Lee NM, Loh HH (1983) Endogenous opioid peptides: comparative evaluation of their receptor affinities in the mouse brain. Life Sci 33:291–294

    Article  PubMed  CAS  Google Scholar 

  • Gianoulakis C, Gupta A (1986) Inbred strains of mice with variable sensitivity to ethanol exhibit differences in the content and processing of beta-endorphin. Life Sci 39:2315–2325

    Article  PubMed  CAS  Google Scholar 

  • Goldstein A, Tachibana S, Lowney LI, Hunkapiller M, Hood L (1979) Dynorphin-(1–13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci 76:6666–6670

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs SC, Joppa M (2001) Dissociation of arousal-like from anxiogenic-like actions of brain corticotropin-releasing factor receptor ligands in rats. Behav Brain Res 122:43–50

    Article  PubMed  CAS  Google Scholar 

  • Heyser CJ, Roberts AJ, Schulteis G, Koob GF (1999) Central administration of an opiate antagonist decreases oral ethanol self-administration in rats. Alcohol Clin Exp Res 23:1468–1476

    Article  PubMed  CAS  Google Scholar 

  • Hughes J, Smith T, Morgan B, Fothergill L (1975a) Purification and properties of enkephalin—the possible endogenous ligand for the morphine receptor. Life Sci 16:1753–1758

    Article  PubMed  CAS  Google Scholar 

  • Hughes J, Smith TW, Kosterlitz HW (1975b) Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258:577–579

    Article  PubMed  CAS  Google Scholar 

  • Imperato A, Di Chiara G (1986) Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219–228

    PubMed  CAS  Google Scholar 

  • Kang-Park MH, Kieffer BL, Roberts AJ, Siggins GR, Moore SD (2007) Presynaptic delta opioid receptors regulate ethanol actions in central amygdala. J Pharmacol Exp Ther 320:917–925

    Article  PubMed  CAS  Google Scholar 

  • Keith LD, Crabbe JC, Robertson LM, Kendall JW (1986) Ethanol-stimulated endorphin and corticotropin secretion in vitro. Brain Res 367:222–229

    Article  PubMed  CAS  Google Scholar 

  • Kendrick KM (1990) Microdialysis measurement of in vivo neuropeptide release. J Neurosci Methods 34:35–46

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2009) Brain stress systems in the amygdala and addiction. Brain Res 1293:61–75

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Volkow ND (2009) Neurocircuitry of addiction. Neuropsychopharmacology 35:217–238

    Article  Google Scholar 

  • Lam MP, Marinelli PW, Bai L, Gianoulakis C (2008) Effects of acute ethanol on opioid peptide release in the central amygdala: an in vivo microdialysis study. Psychopharmacology (Berl) 201:261–271

    Article  CAS  Google Scholar 

  • Lam MP, Nurmi H, Rouvinen N, Kiianmaa K, Gianoulakis C (2010) Effects of acute ethanol on β-endorphin release in the nucleus accumbens of selectively bred lines of alcohol-preferring AA and alcohol-avoiding ANA rats. Psychopharmacology (Berl) 208:121–130

    Article  CAS  Google Scholar 

  • Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW (1977) Endogenous opioid peptides: multiple agonists and receptors. Nature 267:495–499

    Article  PubMed  CAS  Google Scholar 

  • Maidment NT, Brumbaugh DR, Rudolph E, Erdelyi E, Evans CJ (1989) Microdialysis of extracellular endogenous opioid peptides from rat brain in vivo. Neuroscience 33:549–557

    Article  PubMed  CAS  Google Scholar 

  • Maidment NT, Evans CJ, Robinson TE, Justice JRJ (1991) Measurement of extracellular neuropeptides in the brain: microdialysis linked to solid-phase radioimmunoassays with sub-femtomole limits of detection microdialysis in the neurosciences. Elsevier, New York, pp 275–302

    Google Scholar 

  • Marinelli PW, Gianoulakis C, Quirion R (2003) A microdialysis profile of beta-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration. Psychopharmacology (Berl) 169:60–67

    Article  CAS  Google Scholar 

  • Marinelli PW, Bai L, Quirion R, Gianoulakis C (2005) A microdialysis profile of Met-enkephalin release in the rat nucleus accumbens following alcohol administration. Alcohol Clin Exp Res 29:1821–1827

    Article  PubMed  CAS  Google Scholar 

  • Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine- and nalorphine-like drugs in the nondepedent and morphine-dependent chronic spinal dogs. J Pharmacol Exp Ther 197:517–532

    PubMed  CAS  Google Scholar 

  • Merchenthaler I, Vigh S, Petrusz P, Schally AV (1982) Immunocytochemical localization of corticotropin-releasing factor (CRF) in the rat brain. Am J Anat 165:385–396

    Article  PubMed  CAS  Google Scholar 

  • Merlo-Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF, Weiss F (1995) Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci 15:5439–5447

    PubMed  CAS  Google Scholar 

  • Olive MF, Koenig HN, Nannini MA, Hodge CW (2001) Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine, and amphetamine. J Neurosci 21:RC184

    PubMed  CAS  Google Scholar 

  • O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry 49:881–887

    PubMed  Google Scholar 

  • Paul CA, Beltz B, Berger-Sweeney J (2007) Observational methods used to assess rat behavior: general activity. Cold Spring Harb Protoc 2007: pdb.prot4799

  • Paxinos G, Watson C (1996) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  • Richter RM, Zorrilla EP, Basso AM, Koob GF, Weiss F (2000) Altered amygdalar CRF release and increased anxiety-like behavior in Sardinian alcohol-preferring rats: a microdialysis and behavioral study. Alcohol Clin Exp Res 24:1765–1772

    Article  PubMed  CAS  Google Scholar 

  • Robison CL, Meyerhoff JL, Saviolakis GA, Chen WK, Rice KC, Lumley LA (2004) A CRH1 antagonist into the amygdala of mice prevents defeat-induced behavior. Ann NY Acad Sci 1032:324–327

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Seo N, Kobahashi E (2005) The dosing-time dependent effects of intravenous hypnotics in mice. Anesth Analg 101:1706–1708

    Article  PubMed  Google Scholar 

  • Stoessl AJ (1994) Dopamine D1 receptor agonist-induced grooming is blocked by the opioid receptor antagonist naloxone. Eur J Pharmacol 259:301–303

    Article  PubMed  CAS  Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 213:1394–1397

    Article  PubMed  CAS  Google Scholar 

  • Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

These studies were funded through grants from the Natural Sciences and Engineering Research Council of Canada (NSERC). The authors would like to thank Mrs. Mira Thakur, Mr. Samuel Jarjour and Ms. Stephanie Grella for proofing the manuscript.

Author information

Authors and Affiliations

  1. Department of Physiology, McGill University, Montreal, Canada

    Minh P. Lam & Christina Gianoulakis

  2. Department of Psychiatry, McGill University, Montreal, Canada

    Christina Gianoulakis

  3. Douglas Mental Health University Institute, 6875 LaSalle boulevard, Verdun, QC, H4H 1R3, Canada

    Christina Gianoulakis

Authors
  1. Minh P. Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Gianoulakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christina Gianoulakis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lam, M.P., Gianoulakis, C. Effects of acute ethanol on corticotropin-releasing hormone and β-endorphin systems at the level of the rat central amygdala. Psychopharmacology 218, 229–239 (2011). https://doi.org/10.1007/s00213-011-2337-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2337-x

Keywords

Search

Navigation