title: Changed accumbal responsiveness to alcohol in rats pre-treated with nicotine or the cannabinoid receptor agonist WIN 55,212-2.
abstract: Alcohol, nicotine, and cannabinoid acutely increase the activity of the mesolimbic dopamine (DA) pathway. Although polysubstance consumption is a common pattern of abuse in humans, little is known about dopamine release following pre-exposure to these drugs. The purpose of this study was to test whether alcohol-induced dopamine release into the nucleus accumbens (NAc) shell is modified by different pre-treatments: water (i.g.), alcohol (1 g/kg, i.g.), nicotine (0.4 mg/kg, s.c.), and WIN 55,212-2 (1 mg/kg, s.c.). Male Wistar rats were treated (i.g.) for 14 days with either water or alcohol. In the following 5 days rats were injected (s.c.) with vehicle, nicotine, or WIN 55,212-2. Finally, a cannula was surgically implanted into the NAc shell and alcohol-induced extracellular dopamine release was monitored in freely moving rats. Alcohol (1 g/kg; i.g.) only increased the release of dopamine when animals were previously treated with water. This DA increase was markedly inhibited by (subchronic) treatment (5 days) with nicotine or WIN 55-212-2 as well as by previous (chronic) exposure to alcohol (14 days). These data demonstrate that pre-treatment with nicotine and the cannabinoid agonist WIN 55,212-2 is able to change the sensitivity of the NAc shell in response to a moderate dose of alcohol. Therefore, cannabinoid and nicotine exposure may have important implications on the rewarding effects of alcohol, because these drugs lead to long-lasting changes in accumbal dopamine transmission.
authors.affiliation: Laboratory of Psychobiology, Faculty of Psychology, Campus de Somosaguas, Complutense University of Madrid, 28223, Madrid, Spain. jalopezm@psi.ucm.es
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López-Moreno
authors.forename: María
authors.initials: M
authors.lastname: Scherma
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.forename: Gustavo
authors.initials: G
authors.lastname: González-Cuevas
authors.forename: Walter
authors.initials: W
authors.lastname: Fratta
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D012201:Reward; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002492:Central Nervous System Depressants; D009025:Morpholines; D009281:Naphthalenes; D018722:Nicotinic Agonists; D000431:Ethanol; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009538:Nicotine; D004298:Dopamine