EFFECTS OF AMISULPRIDE, AN ATYPICAL ANTIPSYCHOTIC WHICH BLOCKS PREFERENTIALLY PRESYNAPTIC DOPAMINE AUTORECEPTORS, ON INTEGRATED FUNCTIONAL CEREBRAL-ACTIVITY IN THE RAT

Amisulpride, a benzamide derivative with an atypical neuroleptic profi le relieves the negative symptoms of schizophrenia when administered a t low doses (50-150 mg). In an attempt to define the anatomical substr ates involved in this action we have studied the effects of amisulprid e on regional cerebral glucose utilisation (RCGU) in the awake Lightly restrained rat, by quantitative autoradiography using [C-14]2-deoxygl ucose ([C-14]2-DG). Amisulpride was administered 1 h before [C-14]2DG i.v. injection, at a dose of 5 mg/kg which resulted in a striatal D, r eceptor occupancy of 10% similar to that induced by doses of this comp ound used for the treatment of negative symptoms of schizophrenia. Ami sulpride induced significant RCGU increases in cortical areas, in visu al relays, in auditory structures and in several limbic structures. Th e pattern of changes in RCGU seen with amisulpride clearly differs fro m that of haloperidol, given at a dose resulting in a similar occupanc y of striatal D-2 receptors (0.01 mg/kg), which was mostly ineffective . The amisulpride-induced activation of RCGU in specific brain areas i nvolved in the control of cognitive functions and motivational and emo tional behavior, may at least in part, explain the efficacy of this co mpound in the treatment of negative symptoms of schizophrenia. (C) 199 7 Elsevier Science B.V.