Nicotine pre-exposure does not potentiate the locomotor or rewarding effects of Δ-9-tetrahydrocannabinol in rats

Abstract

This study assessed the effects of nicotine pre-exposure on subsequent locomotor and rewarding effects of repeated Delta-9-tetrahydrocannabinol administration in Sprague-Dawley rats. Repeated administration of the same dose of Delta-9-tetrahydrocannabinol (0.01-2 mg/kg) did not produce significant tolerance or behavioral sensitization to Delta-9-tetrahydrocannabinol's locomotor effects. An unbiased place conditioning paradigm was then used to obtain a measure of the rewarding effects of Delta-9-tetrahydrocannabinol. Rats received an injection of either Delta-9-tetrahydrocannabinol (0.01-2 mg/kg) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials) of a two-compartment apparatus. Control rats received saline injections associated with both compartments. Significant conditioned place preferences developed with 0.1 mg/kg Delta-9-tetrahydrocannabinol in control rats, but not in nicotine pre-exposed rats. Surprisingly, significant place aversions developed at higher 1 and 2 mg/kg doses of Delta-9-tetrahydrocannabinol in nicotine pre-exposed rats. To the extent that behavioral sensitization may reflect reward processes in drug dependence, the lack of behavioral sensitization on repeated Delta-9-tetrahydrocannabinol administration is consistent with the difficulties usually encountered in demonstrating rewarding or reinforcing effects of Delta-9-tetrahydrocannabinol in rats. The present findings suggest, moreover, that nicotine pre-exposure alters the qualitative nature of rewarding effects and accentuates aversive effects of Delta-9-tetrahydrocannabinol.