Differences between haloperidol- and pimozide-induced withdrawal syndrome: a role for Ca2+ channels.
We investigated the behavioral and biochemical events appearing in rats after withdrawal for 24 h or 8-12 days from two classical neuroleptics, haloperidol and pimozide. The neuroleptics were given for 14 days alone or shortly after injection of the Ca2+ channel blocker nifedipine. We have found that withdrawal effects after haloperidol and pimozide were different. After haloperidol treatment we observed an increase in cortical Ca2+ channel and limbic dopamine D1 receptor density and an increase in spontaneous motor activity and apomorphine-induced hyperactivity and stereotypy. In contrast no biochemical changes were observed during pimozide withdrawal, and locomotor activity and responses to apomorphine were depressed. Co-administration of nifedipine with haloperidol prevented the observed biochemical and behavioral symptoms of withdrawal. Nifedipine administration did not change the depressant effects of pimozide. Our results suggest that the voltage-dependent Ca2+ channel is involved in the observed withdrawal syndrome of neuroleptics, and that the absence of this syndrome after pimozide may be related to its considerable Ca2+ channel-blocking properties.
Antkiewicz-Michaluk
L
L
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Karolewicz
B
B
Michaluk
J
J
Vetulani
J
J
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001058:Apomorphine / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D006220:Haloperidol / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000378:metabolism; D010868:Pimozide / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000517:prevention & control
D014150:Antipsychotic Agents; D015220:Calcium Channels; D017447:Receptors, Dopamine D1; D010868:Pimozide; D009568:Nitrendipine; D009543:Nifedipine; D006220:Haloperidol; D001058:Apomorphine