EFFECTS OF AMPEROZIDE ON PSYCHOSTIMULANT-INDUCED HYPERLOCOMOTION AND DOPAMINE RELEASE IN THE NUCLEUS-ACCUMBENS

N-Ethyl-4-[4',4'-bis(p-fluorophenyl)-butyl]-1-piperazine carboxamide [amperozide (APZ)] is a novel atypical neuroleptic that appears to selectively act on the limbic system. The present study investigated behavioral and biochemical effects of APZ on either d-amphetamine (AMPH)- or cocaine (COC)-treated rats. Behavior was assessed by locomotor activity measurements. Compared to saline controls, APZ (5 and 10 mg/kg, SC) decreased spontaneous locomotion. AMPH (1.0 mg/kg, SC)- or COC (10 mg/kg, IP)-induced hyperlocomotion was markedly reduced by APZ administered 20 min earlier. Biochemical data were obtained by in vivo microdialysis in freely moving animals. APZ dose dependently increased interstitial concentrations of dopamine (DA, +25%) and its metabolite, homovanillic acid (HVA, +20%), in the nucleus accumbens (NAC). While either AMPH or COC alone increased DA levels (450 and 270%, respectively), pretreatment with APZ had no effect on these increases. In contrast, APZ pretreatment dose dependently attenuated the reduction of DA metabolites induced by both AMPH and COC. Thus, APZ blocked hyperlocomotion induced by psychostimulants without producing correlative changes in DA concentrations in the NAC.