DIFFERENCES BETWEEN HALOPERIDOL-INDUCED AND PIMOZIDE-INDUCED WITHDRAWAL SYNDROME - A ROLE FOR CA2+ CHANNELS

We investigated the behavioral and biochemical events appearing in rat s after withdrawal for 24 h or 8-12 days from two classical neurolepti cs, haloperidol and pimozide. The neuroleptics were given for 14 days alone or shortly after injection of the Ca2+ channel blocker nifedipin e. We have found that withdrawal effects after haloperidol and pimozid e were different. After haloperidol treatment we observed an increase in cortical Ca2+ channel and limbic dopamine D-1 receptor density and an increase in spontaneous motor activity and apomorphine-induced hype ractivity and stereotypy. In contrast no biochemical changes were obse rved during pimozide withdrawal, and locomotor activity and responses to apomorphine were depressed. Go-administration of nifedipine with ha loperidol prevented the observed biochemical and behavioral symptoms o f withdrawal. Nifedipine administration did not change the depressant effects of pimozide. Our results suggest that the voltage-dependent Ca 2+ channel is involved in the observed withdrawal syndrome of neurolep tics, and that the absence of this syndrome after pimozide may be rela ted to its considerable Ca2+ channel-blocking properties.