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Keywords:

  • fast cyclic voltammetry;
  • mesolimbic dopamine system;
  • autoreceptor modulation;
  • chronic neuroleptic treatment

Abstract

Fast cyclic voltammetry was used to assess the effects of chronic oral haloperidol treatment (0.7 mg/kg/day for 21 days) on the sensitivity of dopamine autoreceptors in the rat nucleus accumbens both in vivo and in vitro. Evoked dopamine overflow was significantly reduced after chronic haloperidol treatment, but the sensitivity of dopamine overflow to sulpiride, an antagonist at release-inhibiting dopamine autoreceptors, and quinpirole, an agonist at these receptors, was unchanged. The estimated EC50 values for quinpirole and sulpiride (52 and 60 nM respectively) obtained in vitro and the receptor distribution profiles published in the literature suggest that the autoreceptors involved in this modulation are mainly of the D3 subtype. The finding that the reduced dopamine overflow in the nucleus accumbens observed after chronic treatment with a classical neuroleptic is not due to dopamine autoreceptor supersensitivity may therefore be the first functional evidence for unchanged autoreceptor activity in the nucleus accumbens, supporting biochemical findings of a lack of D3 autoreceptor up-regulation after chronic haloperidol treatment. It lends further support to the assumption that the long-term changes occurring during chronic neuroleptic treatment may not lie at the level of presynaptic dopamine receptor regulation.