title: Anxiolytic effects of ethanol are partially related to a reduced expression of adenylyl cyclase 5 but not to μ-opioid receptor activation in rat nucleus accumbens.
abstract: Anxiolytic effects of alcohol participate in the reinforcing properties of the drug, in which nucleus accumbens (NAcc) is implicated. The opioidergic system in NAcc is considered a main pathway involved in the emotional responses of animals: rats microinjected with morphine in NAcc and the systemic administration of μ-opioid receptors (MOR) agonists yield low anxiety scores in the elevated plus maze (EPM), a behavioral test of anxiety. However, the specific participation of NAcc MOR in the anxiolytic effect of ethanol has not been studied. AC5, a cAMP-synthezising adenylyl-cyclase, is highly expressed in NAcc; it is negatively coupled to MOR and has been implicated in anxiety levels of animals. We evaluated the anxiolytic effects of an intra-gastric administration of ethanol (2.5 g/kg) in animals subjected to EPM at 1, 4, and 8 h after drug or water exposure. Locomotion was assayed with the open-field test; we also measured accumbal AC5 and MOR mRNA levels by RT-PCR. After 1 h, ethanol-exposed animals showed anxiolytic-like behavior, as well as decreased and increased AC5 and MOR expression in NAcc, respectively. Intra-accumbal injection of β-funaltrexamine (FNA), a MOR antagonist, did not block ethanol-induced anxiolysis, rather it induced a tendency to increase anxiety levels in the water-exposed group. FNA partially decreased accumbal AC5 expression in ethanol-treated rats. We concluded that AC5 in NAcc is participating in the emotional effects of ethanol; that MOR was not mediating the drug-induced AC5 reduction in NAcc nor the ethanol-induced anxiolysis. MOR only might be involved in basal levels of anxiety of animals.
authors.affiliation: Neurofisiología Molecular, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente, México D.F., Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Morales-Mulia
authors.forename: E
authors.initials: E
authors.lastname: Estrada-Camarena
authors.forename: M I
authors.initials: MI
authors.lastname: Amaya
authors.forename: S
authors.initials: S
authors.lastname: Mejía-Mauríes
authors.forename: I
authors.initials: I
authors.lastname: Sollozo-Dupont
authors.forename: G
authors.initials: G
authors.lastname: Mengod
authors.forename: P
authors.initials: P
authors.lastname: de Gortari
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D000431:Ethanol; D009271:Naltrexone; C024524:beta-funaltrexamine; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V