Exploration of the Primary Reinforcers and Behaviors that are Enhanced by Delta-9-tetrahydrocannabinol (THC) in Male and Female Rats

Humans consume cannabis for the pharmacological effects mediated by the primary psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC). However, there is little evidence to suggest that THC acts as a primary reinforcer in non-human models because the drug alone does not support robust self-administration. We hypothesized that THC may have more potent reinforcement enhancing effects – meaning that THC may enhance the reinforcing effects of other non-drug rewards in a user’s environment. In the present experiments, we explore the effects of THC on operant responding for saccharin (SACC) or a visual stimulus (VS). In all experiments rats were shaped to respond for their assigned reinforcer. Drug challenge tests were conducted every 72 hours, rats were injected with the assigned dose of THC and responding for each reinforcer was measured. Our initial findings indicated possible sex differences between male and female rats – THC injections increased lever-pressing for SACC in male rats but not female rats. However, in follow-up experiments we used a different response (nose-key press instead of lever press) that facilitated operant responding in rats that were different sizes – adult males are significantly more massive than adult females. In that experiment THC enhanced nose-key presses for SACC in both male and female rats across a range of doses. Moreover, this latter experiment confirmed that the effect of THC was motivational in nature, THC injections increased effort to obtain SACC under a progressively increasing schedule of reinforcement (progressive ratio). Finally, using a third operant response (head entry into a receptacle) we demonstrated that THC increased reinforcement by the VS across a range of doses. The present studies indicate that THC acts as a reinforcement enhancer, increasing motivation in male and female rats to obtain both SACC and VS throughout a range of doses. By demonstrating that THC enhances the reinforcing effects of both gustatory and non-gustatory reinforcers, our evidence supports the hypothesis that THC’s effect on the brain facilitates incentive motivation regardless of sensory modality of the reinforcer