Nicotine pre-exposure does not potentiate the locomotor or rewarding effects of Delta-9-tetrahydrocannabinol in rats.
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.
Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. blefoll@intra.nida.nih.gov
Bernard
B
Le Foll
Marcus
M
Wiggins
Steven R
SR
Goldberg
D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
D006213:Hallucinogens; D018722:Nicotinic Agonists; D009538:Nicotine; D013759:Dronabinol