Skip to main content

Advertisement

SpringerLink
Log in

Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations

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

Abstract

Rationale

Angiotensin II, by activation of its brain AT1-receptors, plays an active role as neuromodulator in dopaminergic transmission. These receptors participate in the development of amphetamine-induced behavioral and dopamine release sensitization. Dopamine is involved in cognitive processes and provides connectivity between brain areas related to these processes. Amphetamine by its mimetic activity over dopamine neurotransmission elicits differential responses after acute administration or after re-exposure following long-term withdrawal periods in different cognitive processes.

Objective

The purpose of this study is to evaluate the AT1-receptor involvement in the acute and long-term amphetamine-induced alterations in long-term memory and in cellular-related events.

Methods

Male Wistar rats (250–300 g) were used in this study. Acute effects: Amphetamine (0.5/2.5 mg/kg i.p.) was administered after post-training in the inhibitory avoidance (IA) response. The AT1-receptor blocker Losartan was administered i.c.v. before a single dose of amphetamine (0.5 mg/kg i.p.). Long-term effects: The AT1-receptors blocker Candesartan (3 mg/kg p.o.) was administered for 5 days followed by 5 consecutive days of amphetamine (2.5 mg/kg/day, i.p.). The neuroadaptive changes were evidenced after 1 week of withdrawal by an amphetamine challenge (0.5 mg/kg i.p.). The IA response, the neuronal activation pattern, and the hippocampal synaptic transmission were evaluated.

Results

The impairing effect in the IA response of post-training acute amphetamine was partially prevented by Losartan. The long-term changes induced by repeated amphetamine (resistance to acute amphetamine interference in the IA response, neurochemical altered response, and increased hippocampal synaptic transmission) were prevented by AT1-receptors blockade.

Conclusions

AT1-receptors are involved in the acute alterations and in the neuroadaptations induced by repeated amphetamine associated with neurocognitive processes.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89:121–145

    Article  CAS  PubMed  Google Scholar 

  • Brown DC, Steward LJ, Ge J, Barnes NM (1996) Ability of angiotensin II to modulate striatal dopamine release via the AT1 receptor in vitro and in vivo. Br J Pharmacol 118:414–420

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bush G, Whalen PJ, Rosen BR, Jenike MA, McInerney SC, Rauch SL (1998) The counting Stroop: an interference task specialized for functional neuroimaging—validation study with functional MRI. Hum Brain Mapp 6:270–282

    Article  CAS  PubMed  Google Scholar 

  • Bush G, Luu P, Posner MI (2000) Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 4:215–222

    Article  PubMed  Google Scholar 

  • Cabib S, Castellano C (1997) Impairments produced by amphetamine and stress on memory storage are reduced following a chronic stressful experience. Psychopharmacology (Berl) 129:161–167

    Article  CAS  Google Scholar 

  • Castellano C, Cestari V, Cabib S, Puglisi-Allegra S (1991) Post-training dopamine receptor agonists and antagonists affect memory storage in mice irrespective of their selectivity for D1 or D2 receptors. Behav Neural Biol 56:283–291

    Article  CAS  PubMed  Google Scholar 

  • Cestari V, Castellano C, Cabib S, Puglisi-Allegra S (1992) Strain-dependent effects of post-training dopamine receptor agonists and antagonists on memory storage in mice. Behav Neural Biol 58:58–63

    Article  CAS  PubMed  Google Scholar 

  • Crabbe JC, Alpern HP (1975) d-Amphetamine: disruptive effects on the long-term store of memory and proactive facilitatory effects on learning in inbred mice. Pharmacol Biochem Behav 3:647–652

    Article  CAS  PubMed  Google Scholar 

  • Daubert DL, Meadows GG, Wang JH, Sanchez PJ, Speth RC (1999) Changes in angiotensin II receptors in dopamine-rich regions of the mouse brain with age and ethanol consumption. Brain Res 816:8–16

    Article  CAS  PubMed  Google Scholar 

  • de Souza FA, Sanchis-Segura C, Fukada SY, de Bortoli VC, Zangrossi H, de Oliveira AM Jr (2004) Intracerebroventricular effects of angiotensin II on a step-through passive avoidance task in rats. Neurobiol Learn Mem 81:100–103

    Article  PubMed  Google Scholar 

  • DeNoble VJ, DeNoble KF, Spencer KR, Chiu AT, Wong PC, Timmermans PB (1991) Non-peptide angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor: effect on a renin-induced deficit of a passive avoidance response in rats. Brain Res 561:230–235

    Article  CAS  PubMed  Google Scholar 

  • Dominguez-Meijide A, Villar-Cheda B, Garrido-Gil P, Sierrra-Paredes G, Guerra MJ, Labandeira-Garcia JL (2014) Effect of chronic treatment with angiotensin type 1 receptor antagonists on striatal dopamine levels in normal rats and in a rat model of Parkinson’s disease treated with L-DOPA. Neuropharmacology 76(Pt A):156–168

    Article  CAS  PubMed  Google Scholar 

  • Dwoskin LP, Jewell AL, Cassis LA (1992) DuP 753, a nonpeptide angiotensin II-1 receptor antagonist, alters dopaminergic function in rat striatum. Naunyn Schmiedebergs Arch Pharmacol 345:153–159

    Article  CAS  PubMed  Google Scholar 

  • Eldred KC, Palmiter RD (2013) Amphetamine-induced sensitization has little effect on multiple learning paradigms and fails to rescue mice with a striatal learning defect. PLoS One 8, e59964

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fukushima H, Zhang Y, Archbold G, Ishikawa R, Nader K, Kida S (2014) Enhancement of fear memory by retrieval through reconsolidation. Elife 3, e02736

    Article  PubMed Central  PubMed  Google Scholar 

  • Gabach LA, Carlini VP, Monti MC, Maglio LE, De Barioglio SR, Perez MF (2013) Involvement of nNOS/NO/sGC/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: does phosphodiesterase 5 inhibition help to drug vulnerability? Psychopharmacology (Berl) 229:41–50

    Article  CAS  Google Scholar 

  • Herdegen T, Leah JD (1998) Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 28:370–490

    Article  CAS  PubMed  Google Scholar 

  • Hoebel BG, Rada P, Mark GP, Hernandez L (1994) The power of integrative peptides to reinforce behavior by releasing dopamine. Ann N Y Acad Sci 739:36–41

    Article  CAS  PubMed  Google Scholar 

  • Ito R, Canseliet M (2010) Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning. Neuropsychopharmacology 35:1440–1452

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • James DT (1975) Posttrial d-amphetamine sulfate and one-trail learning in mice. J Comp Physiol Psychol 89:626–635

    Article  CAS  PubMed  Google Scholar 

  • Jenkins TA, Chai SY, Mendelsohn FA (1997) Effect of angiotensin II on striatal dopamine release in the spontaneous hypertensive rat. Clin Exp Hypertens 19:645–658

    Article  CAS  PubMed  Google Scholar 

  • Kaminsky O, Klenerova V, Stohr J, Sida P, Hynie S (2001) Differences in the behaviour of Sprague-Dawley and Lewis rats during repeated passive avoidance procedure: effect of amphetamine. Pharmacol Res 44:117–122

    Article  CAS  PubMed  Google Scholar 

  • Kerns JG, Cohen JD, MacDonald AW 3rd, Cho RY, Stenger VA, Carter CS (2004) Anterior cingulate conflict monitoring and adjustments in control. Science 303:1023–1026

    Article  CAS  PubMed  Google Scholar 

  • Kokkinidis L (1983) The effects of chronic amphetamine administration on the acquisition and extinction of an active and passive avoidance response in mice. Pharmacol Biochem Behav 19:593–598

    Article  CAS  PubMed  Google Scholar 

  • Koller M, Krause HP, Hoffmeister F, Ganten D (1979) Endogenous brain angiotensin II disrupts passive avoidance behavior in rats. Neurosci Lett 14:71–75

    Article  CAS  PubMed  Google Scholar 

  • Labandeira-Garcia JL, Rodriguez-Pallares J, Villar-Cheda B, Rodriguez-Perez AI, Garrido-Gil P, Guerra MJ (2011) Aging, Angiotensin system and dopaminergic degeneration in the substantia nigra. Aging Dis 2:257–274

    PubMed Central  PubMed  Google Scholar 

  • Lee EH, Ma YL, Wayner MJ, Armstrong DL (1995) Impaired retention by angiotensin II mediated by the AT1 receptor. Peptides 16:1069–1071

    Article  CAS  PubMed  Google Scholar 

  • Leri F, Nahas E, Henderson K, Limebeer CL, Parker LA, White NM (2013) Effects of post-training heroin and d-amphetamine on consolidation of win-stay learning and fear conditioning. J Psychopharmacol 27:292–301

    Article  PubMed  Google Scholar 

  • Llano Lopez LH, Caif F, Garcia S, Fraile M, Landa AI, Baiardi G, Lafuente JV, Braszko JJ, Bregonzio C, Gargiulo PA (2012) Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats. Pharmacol Rep 64:54–63

    Article  CAS  PubMed  Google Scholar 

  • MacDonald AW 3rd, Cohen JD, Stenger VA, Carter CS (2000) Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science 288:1835–1838

    Article  CAS  PubMed  Google Scholar 

  • Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Pinilla E, Rodriguez-Perez AI, Navarro G, Aguinaga D, Moreno E, Lanciego JL, Labandeira-Garcia JL, Franco R (2015) Dopamine D2 and angiotensin II type 1 receptors form functional heteromers in rat striatum. Biochem Pharmacol 96:131–142

    Article  CAS  PubMed  Google Scholar 

  • McGaugh JL (1973) Drug facilitation of learning and memory. Annu Rev Pharmacol 13:229–241

    Article  CAS  PubMed  Google Scholar 

  • Mendelsohn FA, Jenkins TA, Berkovic SF (1993) Effects of angiotensin II on dopamine and serotonin turnover in the striatum of conscious rats. Brain Res 613:221–229

    Article  CAS  PubMed  Google Scholar 

  • Morgan JI, Curran T (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 14:421–451

    Article  CAS  PubMed  Google Scholar 

  • Morgan JM, Routtenberg A (1977) Angiotensin injected into the neostriatum after learning disrupts retention performance. Science 196:87–89

    Article  CAS  PubMed  Google Scholar 

  • Narayanaswami V, Somkuwar SS, Horton DB, Cassis LA, Dwoskin LP (2013) Angiotensin AT1 and AT2 receptor antagonists modulate nicotine-evoked [(3)H]dopamine and [(3)H]norepinephrine release. Biochem Pharmacol 86:656–665

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nelson A, Killcross S (2006) Amphetamine exposure enhances habit formation. J Neurosci 26:3805–3812

    Article  CAS  PubMed  Google Scholar 

  • Parent A (1990) Extrinsic connections of the basal ganglia. Trends Neurosci 13:254–258

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2009) The rat brain in stereotaxic coordinates. Elsevier, Oxford

    Google Scholar 

  • Paz MC, Assis MA, Cabrera RJ, Cancela LM, Bregonzio C (2011) The AT(1) angiotensin II receptor blockade attenuates the development of amphetamine-induced behavioral sensitization in a two-injection protocol. Synapse 65:505–512

    Article  CAS  PubMed  Google Scholar 

  • Paz MC, Marchese NA, Cancela LM, Bregonzio C (2013) Angiotensin II AT(1) receptors are involved in neuronal activation induced by amphetamine in a two-injection protocol. Biomed Res Int 2013:534817

    PubMed Central  PubMed  Google Scholar 

  • Paz MC, Marchese NA, Stroppa MM, Gerez de Burgos NM, Imboden H, Baiardi G, Cancela LM, Bregonzio C (2014) Involvement of the brain renin-angiotensin system (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol. Behav Brain Res 272:314–323

    Article  CAS  PubMed  Google Scholar 

  • Perez MF, Gabach LA, Almiron RS, Carlini VP, De Barioglio SR, Ramirez SR, Ramirez OA (2010) Different chronic cocaine administration protocols induce changes on dentate gyrus plasticity and hippocampal dependent behavior. Synapse 64:742–753

    CAS  PubMed  Google Scholar 

  • Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274–285

    Article  CAS  PubMed  Google Scholar 

  • Pierce RC, Kalivas PW (1997) A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev 25:192–216

    Article  CAS  PubMed  Google Scholar 

  • Puglisi-Allegra S, Cestari V, Cabib S, Castellano C (1994) Strain-dependent effects of post-training cocaine or nomifensine on memory storage involve both D1 and D2 dopamine receptors. Psychopharmacology (Berl) 115:157–162

    Article  CAS  Google Scholar 

  • Raghavendra V, Chopra K, Kulkarni SK (1999) Brain renin angiotensin system (RAS) in stress-induced analgesia and impaired retention. Peptides 20:335–342

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW, Ersche KD, Everitt BJ (2008) Drug addiction and the memory systems of the brain. Ann N Y Acad Sci 1141:1–21

    Article  CAS  PubMed  Google Scholar 

  • Robinson TE, Kolb B (1997) Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J Neurosci 17:8491–8497

    CAS  PubMed  Google Scholar 

  • Robinson TE, Kolb B (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47(Suppl 1):33–46

    Article  CAS  PubMed  Google Scholar 

  • Saavedra JM (1992) Brain and pituitary angiotensin. Endocr Rev 13:329–380

    Article  CAS  PubMed  Google Scholar 

  • Saavedra JM, Ando H, Armando I, Baiardi G, Bregonzio C, Juorio A, Macova M (2005) Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. Regul Pept 128:227–238

    Article  CAS  PubMed  Google Scholar 

  • Schmidt ED, Tilders FJ, Binnekade R, Schoffelmeer AN, De Vries TJ (1999) Stressor- or drug-induced sensitization of the corticosterone response is not critically involved in the long-term expression of behavioural sensitization to amphetamine. Neuroscience 92:343–352

    Article  CAS  PubMed  Google Scholar 

  • Seliger DL (1977) Passive avoidance learning in the rat as functions of d-amphetamine dosage and shock intensity. Psychopharmacology (Berl) 54:241–242

    Article  CAS  Google Scholar 

  • Simon NW, Setlow B (2006) Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: implications for drug addiction. Neurobiol Learn Mem 86:305–310

    Article  CAS  PubMed  Google Scholar 

  • Simonnet G, Giorguieff-Chesselet MF (1979) Stimulating effect of angiotensin II on the spontaneous release of newly synthesized [3H]dopamine in rat striatal slices. Neurosci Lett 15:153–158

    Article  CAS  PubMed  Google Scholar 

  • Teyler TJ, DiScenna P (1987) Long-term potentiation. Annu Rev Neurosci 10:131–161

    Article  CAS  PubMed  Google Scholar 

  • Tilders FJ, Schmidt ED (1999) Cross-sensitization between immune and non-immune stressors. A role in the etiology of depression? Adv Exp Med Biol 461:179–197

    Article  CAS  PubMed  Google Scholar 

  • Tse MT, Cantor A, Floresco SB (2011) Repeated amphetamine exposure disrupts dopaminergic modulation of amygdala-prefrontal circuitry and cognitive/emotional functioning. J Neurosci 31:11282–11294

    Article  CAS  PubMed  Google Scholar 

  • van den Buuse M, Zheng TW, Walker LL, Denton DA (2005) Angiotensin-converting enzyme (ACE) interacts with dopaminergic mechanisms in the brain to modulate prepulse inhibition in mice. Neurosci Lett 380:6–11

    Article  PubMed  Google Scholar 

  • Vanderschuren LJ, Kalivas PW (2000) Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl) 151:99–120

    Article  CAS  Google Scholar 

  • Vanderschuren LJ, Schmidt ED, De Vries TJ, Van Moorsel CA, Tilders FJ, Schoffelmeer AN (1999) A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization in rats. J Neurosci 19:9579–9586

    CAS  PubMed  Google Scholar 

  • Villar-Cheda B, Rodriguez-Pallares J, Valenzuela R, Munoz A, Guerra MJ, Baltatu OC, Labandeira-Garcia JL (2010) Nigral and striatal regulation of angiotensin receptor expression by dopamine and angiotensin in rodents: implications for progression of Parkinson’s disease. Eur J Neurosci 32:1695–1706

    Article  PubMed  Google Scholar 

  • Villar-Cheda B, Dominguez-Meijide A, Valenzuela R, Granado N, Moratalla R, Labandeira-Garcia JL (2014) Aging-related dysregulation of dopamine and angiotensin receptor interaction. Neurobiol Aging 35:1726–1738

    Article  CAS  PubMed  Google Scholar 

  • White FJ, Kalivas PW (1998) Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol Depend 51:141–153

    Article  CAS  PubMed  Google Scholar 

  • Wolf ME (2002) Addiction: making the connection between behavioral changes and neuronal plasticity in specific pathways. Mol Interv 2:146–157

    Article  CAS  PubMed  Google Scholar 

  • Zhuo J, Moeller I, Jenkins T, Chai SY, Allen AM, Ohishi M, Mendelsohn FA (1998) Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors. J Hypertens 16:2027–2037

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from CONICET 11220120100373CO-KB1, SECyT, FONCyT PRESTAMO BID PICT 2476. The authors are grateful to Estela Salde and Lorena Mercado for their laboratory technical assistance.

Author information

Author notes

    Authors and Affiliations

    1. Instituto de Farmacología Experimental Córdoba (IFEC-CONICET) Departamento de Farmacología, Facultad de Ciencias Químicas Universidad Nacional de Córdoba, Córdoba, Argentina

      Natalia Andrea Marchese, Emilce Artur de laVillarmois, Osvaldo Martin Basmadjian, Mariela Fernanda Perez & Claudia Bregonzio

    2. Laboratorio de Neurofarmacología, (IIBYT-CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina

      Gustavo Baiardi

    Authors
    1. Natalia Andrea Marchese
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Emilce Artur de laVillarmois
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Osvaldo Martin Basmadjian
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Mariela Fernanda Perez
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Gustavo Baiardi
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Claudia Bregonzio
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Mariela Fernanda Perez.

    Ethics declarations

    Conflict of interests

    The authors declare that they have no competing interests.

    Ethical approval

    All procedures were handled in accordance with the NIH Guide for the Care and Use of Laboratory Animals as approved by the Animal Care and Use Committee of the Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina (RES 46 2015).

    Additional information

    Natalia Andrea Marchese and Emilce Artur de laVillarmois contributed equally to this work.

    Electronic supplementary materials

    Below is the link to the electronic supplementary material.

    Supplementary Table 1

    Step-through latencies 1. Statistical distribution values for step-through latencies in the training session of all experimental groups submitted to the passive avoidance test. Values are in seconds. All animals exceeding 60 s were dismissed from the statistical analyses. (DOC 52 kb)

    Supplementary Table 2

    Fos-immunoreactivity analysis. Overall statistical results (F values) obtained in the two way ANOVA for Fos-IR cells patterns. (DOC 54 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Marchese, N.A., Artur de laVillarmois, E., Basmadjian, O. et al. Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations. Psychopharmacology 233, 795–807 (2016). https://doi.org/10.1007/s00213-015-4153-1

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00213-015-4153-1

    Keywords

    Search

    Navigation