DOPAMINE AUTORECEPTOR SENSITIVITY IS UNCHANGED IN RAT NUCLEUS-ACCUMBENS AFTER CHRONIC HALOPERIDOL TREATMENT - AN IN-VIVO AND IN-VITRO VOLTAMMETRIC STUDY

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 an d in vitro. Evoked dopamine overflow was significantly reduced after c hronic haloperidol treatment, but the sensitivity of dopamine overflow to sulpiride, an antagonist at release-inhibiting dopamine autorecept ors, and quinpirole, an agonist at these receptors, was unchanged, The estimated EC(50) values for quinpirole and sulpiride (52 and 60 nM re spectively) obtained in vitro and the receptor distribution profiles p ublished in the literature suggest that the autoreceptors involved in this modulation are mainly of the D-3 subtype. The finding that the re duced dopamine overflow in the nucleus accumbens observed after chroni c treatment with a classical neuroleptic is not due to dopamine autore ceptor supersensitivity may therefore be the first functional evidence for unchanged autoreceptor activity in the nucleus accumbens, support ing biochemical findings of a lack of D-3 autoreceptor up-regulation a fter chronic haloperidol treatment. It lends further support to the as sumption that the long-term changes occurring during chronic neurolept ic treatment may not lie at the level of presynaptic dopamine receptor regulation.