title: Alpha1-adrenergic drugs affect the development and expression of ethanol-induced behavioral sensitization.
abstract: According to the incentive sensitization theory, addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems. After repeated ethanol administration, some animals develop psychomotor sensitization, a phenomenon which occurs simultaneously with the incentive sensitization. Recent evidence suggests the involvement of norepinephrine (NE) in drug addiction, with a critical role in the ethanol reinforcing properties. In this study we evaluated the influence of an agonist (phenylephrine) and an antagonist (prazosin) of alpha1-adrenergic receptors on the development and expression of behavioral sensitization to ethanol. Male Swiss mice, previously treated with ethanol or saline, were challenged with the combined administration of ethanol (or saline) with alpha1-adrenergic drugs. Prazosin (0.1; 0.5 and 1.0 mg/kg) and phenylephrine (1.0 and 2.0 mg/kg) administration blocked the expression of behavioral sensitization to ethanol. In another set of experiments, mice treated with 0.5mg/kg of prazosin+ethanol did not present the development of behavioral sensitization. However, when challenged with ethanol alone, they showed the same sensitized levels of locomotor activity of those presented by mice previously treated with ethanol and saline. Phenylephrine (1.0 mg/kg) treatment did not affect the development of behavioral sensitization. Based on this data, we concluded that the alteration of alpha1-adrenergic receptors functioning, by the administration agonists or antagonists, affected the locomotor sensitization to the stimulant effect of ethanol, suggesting that the normal functioning of the noradrenergic system is essential to its development and expression.
authors.affiliation: Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Napoleao de Barros, 925, São Paulo 04024-002, Brazil.
authors.forename: Andrezza Kyunmi
authors.initials: AK
authors.lastname: Kim
authors.forename: Maria Lucia Oliveira
authors.initials: ML
authors.lastname: Souza-Formigoni
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D010656:Phenylephrine; D000431:Ethanol; D011224:Prazosin
keywords: ANOVA; Alpha1-adrenergic receptor; Behavioral sensitization; ETOH; Ethanol; LC; Mice; NAc; NE; PFC; Phen; Phenylephrine; Praz; Prazosin; S.E.M.; Sal; VTA; analyses of variance; ethanol; locus coeruleus; norepinephrine; nucleus accumbens; phenylephrine; prazosin; prefrontal cortex; saline; standard error of the mean; ventral tegmental area