Calmodulin inhibitor trifluoperazine attenuates the development and expression of morphine-induced conditioned place preference in rats.
The effect of trifluoperazine, a calmodulin inhibitor, on morphine-induced conditioned place preference was examined in rats. Morphine (5, 10 mg/kg, i.p.) produced significant place preference for the drug-associated place. Trifluoperazine significantly suppressed the development as well as the expression of morphine-induced place preference in a dose-dependent manner, but it neither produced place preference or aversion, nor affected locomotor activity. Injection of 0.5 and 1.0 mg/kg apomorphine, a dopamine receptor agonist, did not alter the inhibition by trifluoperazine of morphine-induced place preference. Verapamil, at the dose that failed to change the place preference induced by morphine, enhanced the inhibition by trifluoperazine of morphine-induced place preference. These findings provide the first demonstration that trifluoperazine attenuates morphine-induced conditioned place preference in rats. The action of trifluoperazine might be produced through its inhibition of calmodulin, but is probably not related to dopamine receptor blockade.
Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100083, PR China.
Xiang-Feng
XF
Ye
Ying
Y
Lu
Pan
P
Zhang
Jian-Hui
JH
Liang
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D065127:Dopamine D2 Receptor Antagonists; D009294:Narcotics; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014268:Trifluoperazine; D009020:Morphine; D014700:Verapamil; D001058:Apomorphine