Antagonism by pimozide of olanzapine-induced hypothermia.
The atypical antipsychotic olanzapine (2.5-20 mg/kg) produced hypothermia in rats. The decrease in rectal temperature caused by olanzapine (2.5-20 mg/kg) was blocked by the selective dopamine D2 receptor antagonist pimozide (0.5 and 1 mg/kg) but not by the dopamine D1 receptor antagonist SCH 23390 (0.5 and 1 mg/kg). The dopamine D1/D2 receptor agonist apomorphine (3 mg/kg) and the selective dopamine D2 receptor agonist talipexole (0.5 mg/kg) produced hypothermia in rats. Olanzapine (10 and 20 mg/kg) significantly blocked hypothermia produced by both apomorphine and talipexole while the lower doses (2.5 and 5 mg/kg) of olanzapine failed to block it. The present results demonstrate that olanzapine behaves as a partial agonist at brain DA D2 receptor populations involved in thermoregulation in the rat.
Ninan
I
I
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001569:Benzodiazepines; D001831:Body Temperature / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D000077152:Olanzapine; D010868:Pimozide / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D014150:Antipsychotic Agents; D001381:Azepines; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D001569:Benzodiazepines; D010868:Pimozide; D010890:Pirenzepine; C024763:talipexole; D001058:Apomorphine; D000077152:Olanzapine