title: Nucleus accumbens dopamine D₁ receptors regulate the expression of ethanol-induced behavioural sensitization.
abstract: Repeated ethanol administration may induce behavioural sensitization, defined as a progressive potentiation of locomotor stimulant effects. This process is associated with neuroadaptations in the mesolimbic pathway and the nucleus accumbens. The aim of the present study was to analyse dopamine D₁ receptor (D₁R) participation in locomotor response to an agonist and an antagonist of the D₁R in mice with different levels of sensitization to ethanol. In three separate experiments, mice received administrations of 2.2 g/kg ethanol or saline every other day for 10 d. According to their locomotor response on the last day, ethanol-treated animals were classified into two groups: sensitized or non-sensitized. After the treatment, mice were challenged with 4 or 8 mg/kg SKF-38393 (i.p.), a D₁R agonist (expt 1); or with 0.01 or 0.1 mg/kg SCH-23390 (i.p.), a D₁R antagonist, followed by 2.2 g/kg ethanol (i.p.) administration (expt 2). In expt 3, mice were challenged with intra-accumbens (intra-NAc) SKF-38393 (1 μg/side, in 0.2 μl), and with intra-NAc SCH-23390 (3 μg/side, in 0.2 μl) followed by 2.2 g/kg ethanol (i.p.). Although the i.p. administration of SKF-38393 did not affect the locomotion of mice, the intra-NAc administration of SKF-38393 significantly increased the locomotor activity in sensitized mice, suggesting that sensitized mice present functionally hyperresponsive D₁Rs in the NAc. Both i.p. and intra-NAc administration of SCH-23390 blocked the expression of ethanol sensitization, suggesting that the activation of NAc D₁Rs seems to be essential for the expression of ethanol sensitization.
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Karina Possa
authors.initials: KP
authors.lastname: Abrahao
authors.forename: Isabel Marian Hartmann
authors.initials: IM
authors.lastname: Quadros
authors.forename: Maria Lucia Oliveira
authors.initials: ML
authors.lastname: Souza-Formigoni
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D002492:Central Nervous System Depressants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D000431:Ethanol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine