Nucleus accumbens dopamine D₁ receptors regulate the expression of ethanol-induced behavioural sensitization.

Int J Neuropsychopharmacol

Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Published: March 2011

AI Article Synopsis

  • Repeated ethanol exposure can lead to behavioral sensitization, enhancing locomotion, linked to changes in brain pathways like the mesolimbic system.
  • The study assessed how dopamine D₁ receptors (D₁Rs) affect locomotion in mice with varying responses to ethanol by testing both a D₁R agonist and antagonist.
  • Findings indicate that sensitized mice show heightened D₁R activity in the nucleus accumbens, and blocking these receptors can prevent ethanol sensitization effects.

Article 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.

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http://dx.doi.org/10.1017/S1461145710000441DOI Listing

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