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.