Antagonism by SCH 23390 of clozapine-induced hypothermia in the rat.
Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.
Salmi
P
P
Department of Behavioural Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Karlsson
T
T
Ahlenius
S
S
D000662:Amphetamines / Q000037:antagonists & inhibitors; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation; D002839:Chromans / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003024:Clozapine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced*; D007279:Injections, Subcutaneous; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D019257:Quinpirole; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology; D012702:Serotonin Antagonists
D000662:Amphetamines; D001552:Benzazepines; D002839:Chromans; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D012702:Serotonin Antagonists; D019257:Quinpirole; D020891:Raclopride; D010095:Oxotremorine; C065380:A 68930; D003024:Clozapine; D003000:Clonidine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine