Abstract
Rationale
Alcohol stimulates the release of dopamine in the nucleus accumbens (NACB) of rats, mice and humans. There is evidence to suggest that the activation of beta-endorphin (β-EP) in the mesolimbic pathway by alcohol and other drugs of abuse may be associated with the rise in dopamine levels in the NACB.
Objectives
The present studies investigate whether the release of β-EP in the NACB is (1) dependent on the dose of alcohol that is administered, and (2) associated with changes in the extracellular concentrations of the catecholamines dopamine and norepinephrine, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the NACB.
Methods
Male Sprague-Dawley rats were implanted with a microdialysis probe positioned in the shell region of the NACB. Artificial cerebrospinal fluid was pumped at a rate of 2.3 μl/min in awake and freely moving animals and the dialysate was collected at 30-min intervals. After a baseline period, rats were injected intraperitoneally with either physiological saline or one of three doses of alcohol: 0.8, 1.6, or 2.4 g ethanol/kg body weight. The dialysates collected were analyzed with radioimmunoassay, to estimate the content of β-EP; and high performance liquid chromatography, to estimate the content of dopamine, norepinephrine, DOPAC and HVA.
Results
Alcohol induced a dose-dependent increase in the extracellular levels of β-EP and dopamine. However, elevations in the extracellular levels of norepinephrine, DOPAC and HVA did not reach significance. The largest increase in β-EP and dopamine was observed with the 2.4 g/kg dose.
Conclusion
The alcohol-induced release of β-EP and dopamine in the NACB is dose-dependent, where the highest dose resulted in more pronounced concentrations in the dialysate. Furthermore, the increase in the extracellular levels of dopamine appeared to occur at an earlier time point following alcohol administration, than for β-EP. These results suggest that alcohol stimulates dopamine and β-EP in the NACB, but probably does so via independent mechanisms.
Similar content being viewed by others
References
Acquas E, Meloni M, DiChiara G (1993) Blockade of δ-opioid receptors in the nucleus accumbens prevents ethanol-induced stimulation of dopamine release. Eur J Pharmacol 230:239–241
Boyadjieva NI, Sarkar DK (1995) Effects of dopamine D1 and D2 receptor agonists and antagonists on basal and ethanol-modulated beta-endorphin secretion from hypothalamic neurons in primary cultures. J Neuroendocrinol 1995:11–819
Bozarth MA, Wise RA (1981) Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci 28:551–555
Brown ZW, Amit Z (1977) The effects of selective cathecholamine depletions by 6-hydroxydopamine on ethanol preference in rats. Neurosci Lett 5:333–336
Carlsson A, Magnusson T, Svensson T, Waldeck B (1973) Effect of ethanol on the metabolism of brain catecholamines. Psychopharmacologia 30:27–36
de Waele J-P, Papachristou DN, Gianoulakis C (1992) The alcohol preferring C57BL/6 mice present an enhanced sensitivity of hypothalamic β-endorphin system to ethanol than the alcohol-avoiding DBA/2 mice. J Pharmacol Exp Ther 261:788–794
de Waele J-P, Gianoulakis C (1993) Effects of single and repeated exposures to ethanol on hypothalamic β-endorphin and CRH release by the C57BL/6 and DBA/2 strains of mice. Neuroendocrinology 57:700–709
de Waele J-P, Kiianmaa K, Gianoulakis C (1994) Spontaneous and ethanol-stimulated in vitro release of β-endorphin by the hypothalamus of AA and ANA rats. Alcohol Clin Exp Res 18:1468–1473
Devine DP, Leone P, Pocock D, Wise RA (1993) Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in the modulation of basal mesolimbic dopamine release: in vivo microdialysis studies. J Pharmacol Exp Ther 266:1236–1246
DiChiara G, Imperato A (1985) Ethanol preferentially stimulates dopamine release in the nucleus accumbens of freely-moving rats. Eur J Pharmacol 115:131–132
DiChiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278
Fahlke C, Hansen S, Engel JA, Hard E (1994) Effects of ventral striatal 6-OHDA lesions or amphetamine sensitization on oral self-administration of alcohol in the rat. Pharmacol Biochem Behav 47:345–349
Feenstra MGP, Botterblom MHA, Mastenbroek S (2000) dopamine and noradrenaline efflux in prefrontal cortex in the light and dark period: effects of novelty and handling and comparison to the nucleus accumbens. Neuroscience 100:741–748
Files FJ, Denning CF, Samson HH (1998) Effects of the atypical antipsychotic remoxipride on alcohol self-administration. Pharmacol Biochem Behav 59:281–285
Froehlich JC, Li T-K (1994) Opioid involvement in alcohol drinking. Ann NY Acad Sci 739:156–167
Gatto GJ, McBride WJ, Murphy JM, Lumeng L, Li T-K (1994) Ethanol self-infusion into the ventral tegmental area by alcohol preferring (P) rats. Alcohol 11:557–564
Gianoulakis C (1990) Characterization of the effects of acute ethanol administration on the release of β-endorphin peptides by the rat hypothalamus. Eur J Pharmacol 180:21–29
Gianoulakis C (2001) Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. J Psychiatr Neurosci 26:304–318
Gianoulakis C, Gupta A (1986) Inbred strains of mice with variable sensitivity to ethanol exhibit differences in content and processing of β-endorphin. Life Sci 39:2315–2325
Gianoulakis C, Marinelli PW, Kiianmaa K (1999) Absence of a direct in vitro effect of ethanol on β-endorphin release by the nucleus accumbens of AA and ANA lines of rats. Soc Neurosci Abstr 25:1576
Gonzales RA, Weiss F (1998) Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. J Neurosci 18:10663–10671
Grenhoff J, Nisell M, Ferre S, Aston-Jones G, Svensson TH (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. J Neural Transm [Gen Sect] 93:11–25
Hakan RL, Henriksen SJ (1989) Opiate influences on nucleus accumbens electrophysiology: dopamine and non-dopamine mechanisms. J Neurosci 9:3538–3546
Heyser CJ, Roberts AJ, Schulteis G, Koob GF (1999) Central administration of an opioid receptor antagonist decreases oral ethanol self-administration in rats. Alcohol Clin Exp Res 23:1468–1476
Hökfelt T, Broberger C, Xu Z-QD, Sergeyev V, Ubink R, Diez M (2000) Neuropeptides—an overview. Neuropharmacology 39:1337–1356
Hunt WA, Majchrowicz E (1974) Alterations in the turnover of brain norepinephrine and dopamine in alcohol-dependent rats. J Neurochem 23:549–552
Hyytiä P, Sinclair JD (1993) Responding for oral ethanol after naltrexone treatment by alcohol preferring AA rats. Alcohol Clin Exp Res 17:631–636
Ikemoto S, McBride WJ, Murphy JM, Lumeng L, Li T-K (1997) 6-OHDA-lesions of the nucleus accumbens disrupt the acquisition but not the maintenance of ethanol consumption in the alcohol preferring P line of rats. Alcohol Clin Exp Res 21:1042–1046
Imperato A, DiChiara G (1986) Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219–228
Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council (1996) Guide for the Care and use of Laboratory Animals. National Academy Press, Washington D.C.
Jiang ZG, North RA (1992) Pre- and postsynaptic inhibition by opioids in rat striatum. J Neurosci 12:356–361
Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12:483–488
Kiianmaa K, Nurmi M, Nykanen I, Sinclair JD (1995) Effect of ethanol on extracellular dopamine in the nucleus accumbens of alcohol-preferring AA and alcohol-avoiding ANA rats. Pharmacol Biochem Behav 52:29–34
Koistinen M, Tuomainen P, Hyytiä P, Kiianmaa K (2001) Naltrexone suppresses ethanol intake in 6-hydroxydopamine treated rats. Alcohol Clin Exp Res 25:1605–1612
Li SJ, Scanlon MN, Jarai Z, Varga K, Gatenberg NS, Lazar-Wesley E, Kunos G (1996) alpha-2-Adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia. Neuroendocrinology 63:275–283
Lundquist F (1957) The determination of ethyl alcohol in blood and tissues. In: Glick D (ed) Methods of biochemical analysis. Interscience Publishers, New York, pp 217–251
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 Publishers, Amsterdam, N.L., pp 275–302
Middaugh LD, Kelley BM, Cuison ER Jr, Groseclose CH (1999) Naltrexone effects on ethanol reward and discrimination in C57BL/6 mice. Alcohol Clin Exp Res 23:456–464
Middaugh LD, Bandy A-LE, Price KL, Malcolm WJ, Kalivas PW (2001) The increase in extracellular dopamine resulting from ethanol consumption by C57BL/6 mice is attenuated by naltrexone. Alcohol Clin Exp Res 25:56A
Myers RD, Robinson DE (1999) Mu and D2 receptor antisense oligonucleotides injected in the nucleus accumbens suppress high alcohol intake in genetic drinking HEP rats. Alcohol 18:225–233
Noel MB, Gratton A (1995) Electrochemical evidence of increased dopamine transmission in prefrontal cortex and nucleus accumbens elicited by ventral tegmental mu-opioid receptor activation in freely behaving rats. Synapse 21:110–122
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:RC184:1–5
O'Neill RD, Fillenz M (1985) Simultaneous monitoring of dopamine release in rat frontal cortex, nucleus accumbens and striatum: effect of drugs, circadian changes and correlations with motor activity. Neuroscience 16:49–55
Pihl RO, Benkelfat C, Boileau I, Assaad J, Leyton M, Trembly R, Dagher A (2001) Acute ethanol consumption increases synaptic dopamine in ventral striatum: a PET/11C-raclopride study in healthy volunteers. Alcohol Clin Exp Res 25:57A
Rasmussen DD, Bryant CA, Boldt BM, Colasurdo EA, Levin N, Wilkinson CW (1998) Acute alcohol effects on opiomelanocortinergic regulation. Alcohol Clin Exp Res 22:789–801
Rassnick S, Pulvirenti L, Koob GF (1992) Oral ethanol self-administration in rats is reduced by the administration of dopamine and glutamate receptor antagonists into the nucleus accumbens. Psychopharmacology 109:92–98
Rassnick S, Stinus L, Koob GF (1993) The effects of 6-hydroxydopamine lesions of the nucleus accumbens and mesolimbic dopamine system on oral-self administration of ethanol in the rat. Brain Res 623:16–24
Raymond V, Lepine J, Giguerre V, Lissitzky JC, Cote J, Labrie F (1981) Parallel stimulation of ACTH, beta-LPH+beta-endorphin and alpha-MSH release by alpha-adrenergic agents in the rat anterior pituitary cells in culture. Mol Cell Endocrinol 22:295–303
Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25
Snape BM, Engel JA (1988) Ethanol enhances the calcium-dependent stimulus-induced release of endogenous dopamine from slices of rat striatum and nucleus accumbens in vitro. Neuropsychopharmacology 27:1097–1101
Stromberg MF, Casale M, Volpicelli JR, O'Brien CP (1998) A comparison of the effects of the opioid antagonists naltrexone, naltrindole, and beta-funaltrexamine on ethanol consumption in the rat. Alcohol 15:281–289
Swanson LW (1992) Brain maps: structure of the rat brain. Elsevier, New York
Tizabi Y, Copeland RL Jr, Louis VA, Taylor RE (2002) Effects of combined systemic alcohol and central nicotine administration into ventral tegmental area on dopamine release in the nucleus accumbens. Alcohol Clin Exp Res 26:394–399
Tsingos C, Chrousos G (1995) The neuroendocrinology of the stress response. Gender and alcohol seeking behavior. NIAAA monograph 29. National Institute on Alcohol Abuse and Alcoholism, Bethesda, pp 103–124
Weiss F, Lorang MT, Bloom FE, Koob GF (1993) Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants. J Pharmacol Exp Ther 267:250–267
Wozniak KM, Pert A, Mele A, Linnoila M (1991) Focal applications of alcohol elevates extracellular dopamine in rat brain: a microdialysis study. Brain Res 540:31–40
Yan Q-S (1999) Extracellular dopamine and serotonin after ethanol monitored with 5-minute microdialysis. Alcohol 19:1–7
Yoshimoto K, McBride WJ, Lumeng L, Li T-K (1991) Alcohol stimulates the release of dopamine and serotonin in the nucleus accumbens. Alcohol 9:17–22
Yoshimoto K, McBride WJ, Lumeng L, Li T-K (1992) Ethanol enhances the release of dopamine and serotonin in the nucleus accumbens of HAD and LAD lines of rats. Alcohol Clin Exp Res 16:781–785
Zangen A, Nakash R, Yadid G (1999) Serotonin-mediated increases in extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens: a microdialysis study. J Neurochem 73:2569–2574
Acknowledgements
These experiments were funded through a grant from the Natural Sciences and Engineering Research Council of Canada. Peter Marinelli is supported by a doctoral scholarship from Fonds de la recherche en santé du Québec.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marinelli, P.W., Quirion, R. & Gianoulakis, C. A microdialysis profile of β-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration. Psychopharmacology 169, 60–67 (2003). https://doi.org/10.1007/s00213-003-1490-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-003-1490-2