Nucleus accumbens dopamine D₁ receptors regulate the expression of ethanol-induced behavioural sensitization.
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.
Abrahao
Karina Possa
KP
Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
Quadros
Isabel Marian Hartmann
IM
Souza-Formigoni
Maria Lucia Oliveira
ML
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*
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