Skip to main content

Advertisement

Log in

Effects of acute ethanol on opioid peptide release in the central amygdala: an in vivo microdialysis study

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

Abstract

Rationale

There is experimental evidence that indicates that the endogenous opioid system of the central nucleus of the amygdala (CeA) may mediate some of the reinforcing effects of ethanol. However, the precise interactions of ethanol with the endogenous opioid system at the level of the CeA have not been investigated.

Objectives

The aim of the current study was to investigate the hypothesis that acute systemic ethanol administration will increase the release of endogenous opioid peptides at the level of the CeA in a time- and dose-dependent manner.

Materials and methods

Rats were implanted with a unilateral guide cannula to aim microdialysis probes at the CeA. Intraperitoneal injections of saline and various doses of ethanol (0.8, 1.6, 2.0, 2.4, and 2.8 g ethanol/kg body weight) were administered to the rats. Dialysate samples were collected at 30-min intervals at distinct time points prior to and following treatment. Radioimmunoassays specific for β-endorphin, met-enkephalin, and dynorphin A1–8 were used to determine the effect of ethanol on the content of the opioid peptides in the dialysate.

Results

We report that the 2.8-g/kg dose of ethanol induced a long-lasting increase in β-endorphin release from 60 min onwards following administration and, later, an ongoing increase in dynorphin A1–8 release. None of the ethanol doses tested elicited significant changes in dialysate met-enkephalin content compared to the saline treatment.

Conclusions

Acute systemic ethanol administration induced a dose- and time-dependent increase in β-endorphin and dynorphin A1–8 release at the level of the CeA, which may be involved in ethanol consumption.

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

Access this article

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
Fig. 6

Similar content being viewed by others

Abbreviations

aCSF:

artificial cerebral spinal fluid

ANOVA:

analysis of variance

ACTH:

adrenocorticotrophin hormone

α-MSH:

α-melanocortin stimulating hormone

BAC:

blood alcohol concentration

β-LPH:

β-lipotropin hormone

BLA:

basolateral nucleus of the amygdala

BSA:

bovine serum albumin

CeA:

central nucleus of the amygdala

GABA:

gamma-aminobutyric acid

HPA axis:

hypothalamic-pituitary-adrenal axis

IP:

intraperitoneal

NAC:

nucleus accumbens

RIA:

radioimmunoassay

VTA:

ventral tegmental area

References

  • Akil H, Watson SJ, Young E, Lewis ME, Khachaturian H, Walker MJ (1984) Endogenous opioids: biology and function. Annu Rev Neurosci 7:223–255

    Article  PubMed  CAS  Google Scholar 

  • Alheid G (2003) Extended amygdala and basal forebrain. Ann N Y Acad Sci 985:185–205

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Bals-Kubik R, Herz A, Shippenberg TS (1989) Evidence that the aversive effects of opioid antagonists and kappa-agonists are centrally mediated. Psychopharmacology 98:203–206

    Article  PubMed  CAS  Google Scholar 

  • Blake MJ, Stein EA, Czech DA (1987) Drinking-induced alterations in reward pathways: an in vivo autoradiographic analysis. Brain Res 413:111–119

    Article  PubMed  CAS  Google Scholar 

  • Bodnar RJ, Hadjimarkou MM (2001) Endogenous opiates and behavior: 2001. Peptides 23:2307–2365

    Article  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 

  • Charness M (1989) Ethanol and opioid receptor signalling. Experientia 45:418–428

    Article  PubMed  CAS  Google Scholar 

  • Corbett AD, Paterson SJ, McKnight AT, Magnan J, Kosterlitz HW (1982) Dynorphin 1–8 and dynorphin 1–9 are ligands for the kappa-subtype of opiate receptor. Nature 299:79–81

    Article  PubMed  CAS  Google Scholar 

  • Cowen MS, Lawrence AJ (1999) The role of opioid–dopamine interactions in the induction and maintenance of ethanol consumption. Prog Neuro-psychopharmacol Biol Psychiatry 23:1171–1212

    Article  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 

  • Davis M (1992) The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety. Trends Pharmacol Sci 13:35–41

    Article  PubMed  CAS  Google Scholar 

  • Ding YQ, Kaneko T, Nomura S, Mizumo N (1996) Immunohistochemical localization of mu-opioid receptors in the central nervous system of the rat. J Comp Neurol 367:375–402

    Article  PubMed  CAS  Google Scholar 

  • Finnegan TF, Chen SR, Pan HL (2005) Effect of the {micro} opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala. J Pharmacol Exp Ther 312:441–448

    Article  PubMed  CAS  Google Scholar 

  • Foster KL, McKay PF, Seyoum R, Milbourne D, Yin W, Sarma PV, Cook JM, June HL (2004) GABA(A) and opioid receptors of the central nucleus of the amygdala selectively regulate ethanol-mantained behaviors. Neuropsychopharmacology 29:269–284

    Article  PubMed  CAS  Google Scholar 

  • Froehlich JC, Harts J, Lumeng L, Li T-K (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 

  • Froehlich JC, Zweifel M, Harts J, Lumeng L, Li TK (1991) Importance of d opioid receptors in maintaining high alcohol drinking. Psychopharmacology 103:467–472

    Article  PubMed  CAS  Google Scholar 

  • Funk CK, O’Dell LE, Crawford E, 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 (1996) Implication of endogenous opioids and dopamine in alcoholism: human and basic science studies. Alcohol Alcohol Suppl 1:33–42

    PubMed  CAS  Google Scholar 

  • Gianoulakis C (2004) Endogenous opioids and addiction to alcohol and other drugs of abuse. Curr Top Med Chem 4:39–50

    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 

  • 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

    PubMed  CAS  Google Scholar 

  • Hyytiä P, Koob GF (1995) GABA(A) receptor antagonism in the extended amygdala decreases ethanol self-administration in rats. Eur J Pharmacol 283:151–159

    Article  PubMed  Google Scholar 

  • Hyytiä P, Kiianmaa K (2001) Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats. Alcohol Clin Exp Res 25:25–33

    Article  PubMed  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 239:219–28

    PubMed  CAS  Google Scholar 

  • Jarjour SJ, Gianoulakis C (2006) Acute ethanol exposure alters the levels of opioid peptides in the VTA of the rat. Alcohol Clin Exp Res 30:128A

    Google Scholar 

  • June HL, Cummings R, Eiler WJAI, Foster KL, McKay PF, Seyoum R, Garcia M, McCane S, Grey C, Hawkins SE, Mason D (2004) Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats. Neuropsychopharmacology 29:285–299

    Article  PubMed  CAS  Google Scholar 

  • Kang W, Wilson SP, Wilson MA (2000) Overexpression of proenkephalin in the amygdala potentiates the anxiolytic effects of benzodiazepines. Neuropsychopharmacology 22:77–88

    Article  PubMed  CAS  Google Scholar 

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

    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 

  • Krishnan-Sarin S, Jing SL, Kurtz DL, Zweifel M, Portoghese PS, Li T-K, Froehlich JC (1995) The d opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference. Psychopharmacology 120:177–185

    Article  PubMed  CAS  Google Scholar 

  • Land B, Bruchas M, Lemos J, Xu M, Melief E, Chavkin C (2008) The dysphoric component of stress is encoded by activation of the dynorphin k-opioid system. J Neurosci 28:407–414

    Article  PubMed  CAS  Google Scholar 

  • LeDoux JE (1993) Emotional memory systems in the brain. Behav Brain Res 58:69–79

    Article  PubMed  CAS  Google Scholar 

  • LeDoux JE, Iwata J, Cicchetti P, Reis DJ (1988) Different projections of the central amygdaloid nucleus mediate autonomc and behavioral correlates of conditioned fear. J Neurosci 8:2517–2529

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lundquist F (1957) The determination of ethyl alcohol in blood and tissues. In: Glick D (ed) Methods in biochemical analysis. Interscience, New York, USA, pp 217–251

    Google Scholar 

  • Maidment NT, Evans CJ (1991) Measurement of extracellular neuropeptides in the brain: microdialysis linked to solid-phase radioimmunoassays with sub-femtomole limits of detection. In: Robinson TE, Justice JB Jr (eds) Microdialysis in the neurosciences. Elsevier Science, Amsterdam, The Netherlands, pp 275–302

    Google Scholar 

  • Marchant NJ, Densmore VS, Osborne PB (2007) Coexpression of prodynorphin and corticotropin-releasing hormone in the rat central amygdala: evidence of two distinct endogenous opioid systems in the lateral division. J Comp Neurol 504:702–715

    Article  PubMed  CAS  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 169:60–67

    Article  PubMed  CAS  Google Scholar 

  • Marinelli PW, Gianoulakis C, Quirion R (2004) An in vivo profile of beta-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol. Neuroscience 127:777–784

    Article  PubMed  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 

  • Marinelli PW, Lam M, Bai L, Quirion R, Gianoulakis C (2006) A microdialysis profile of Dynorphin A1–8 release in the rat nucleus accumbens following acohol administration. Alcohol Clin Exp Res 30:982–990

    Article  PubMed  CAS  Google Scholar 

  • Merlo-Pich E, Lorang M, Yeganeh M, de Fonseca FR, 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 

  • Ogilvie KM, Lee S, Rivier C (1997) Role of arginine vasopressin and corticotropin-releasing factor in mediating alcohol-induced adrenocorticotropin and vasopressin secretion in male rats bearing lesions of the paraventricular nuclei. Brain Res 744:83–85

    Article  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 21:1–5

    Google Scholar 

  • Paden CM, Krall S, Lynch WC (1987) Heterogenous distribution and upregulation of m, d and k opioid receptors in the amygdala. Brain Res 418:349–355

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, San Diego

    Google Scholar 

  • Quirion R, Weiss AS, Pert CB (1983) Comparative pharmacological properties and autoradiographic distribution of [3H]Ethylketocyclazine binding sites in rat and guinea pig brain. Life Sci 33:183–186

    Article  PubMed  CAS  Google Scholar 

  • Richter RM, Weiss F (1999) In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse 32:254–261

    PubMed  CAS  Google Scholar 

  • Rivier C (1996) Alcohol stimulates ACTH secretion in the rat: mechanisms of action and interactions with other stimuli. Alcohol Clin Exp Res 20:240–54

    Article  PubMed  CAS  Google Scholar 

  • Roberto M, Madamba SG, Moore SD, Tallent MK, Siggins GR (2003) Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons. Proc Natl Acad Sci U S A 100:2053–2058

    Article  PubMed  CAS  Google Scholar 

  • Roberto M, Schweitzer P, Madamba SG, Stouffer DG, Parsons LH, Siggins GR (2004) Acute and chronic ethanol alter glutamatergic transmission in rat central amygdala: an in vitro and an in vivo analysis. J Neurosci 24:1594–1603

    Article  PubMed  CAS  Google Scholar 

  • Shippenberg TS, Bals-Kubik R, Herz A (1993) Examination of the neurochemical substrates mediating the motivational effects of opioids: role of the mesolimbic dopamine system and D-1 vs. D-2 dopamine receptors. Trends Pharmacol Sci 265:53–59

    CAS  Google Scholar 

  • Zangen A, Herzberg U, Vogel Z, Yadid G (1998) Nociceptive stimulus induces release of endogenous release of b-endorphin in the rat brain. Neuroscience 85:659–662

    Article  PubMed  CAS  Google Scholar 

  • Zhu W, Pan ZZ (2005) Mu-Opioid-mediated inhibition of glutamate synaptic transmission in rat central amygdala neurons. Neuroscience 133:97–103

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Ms. Mira Thakur for proofing the manuscript. These studies were funded through a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christina Gianoulakis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lam, M.P., Marinelli, P.W., Bai, L. et al. Effects of acute ethanol on opioid peptide release in the central amygdala: an in vivo microdialysis study. Psychopharmacology 201, 261–271 (2008). https://doi.org/10.1007/s00213-008-1267-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1267-8

Keywords

Navigation