Blocking CB2 receptors during adolescence impaired one type of reward learning but not another in adult rats

Rats treated with the CB2 receptor antagonist/inverse agonist SR144528 during adolescence (postnatal days 28-41) showed significantly slower acquisition of the Pavlovian autoshaping task in adulthood (F(2,19)=5.964, p=0.010). However, there was no effect on instrumental conditioning, indicating a dissociation between CB2 receptor involvement in different types of reward learning.

Male adolescent rats received low or high doses of the CB2 receptor antagonist SR144528 during postnatal days 28-41. In adulthood, Pavlovian autoshaping (lever pressing in response to reward-associated cues) and instrumental conditioning (lever pressing for direct reward) were assessed.

Most cannabis research focuses on CB1 receptors, but this study shows CB2 receptors also influence brain development during adolescence. The selective impact on Pavlovian but not instrumental learning suggests CB2 receptors shape specific aspects of how the reward system matures.

The dissociation between Pavlovian and instrumental reward learning effects suggests the adolescent CB2 receptor system selectively influences cue-reward associations rather than action-outcome learning, which has implications for understanding vulnerability to cue-triggered substance use behaviors.

Male rats only. Pharmacological antagonism of CB2 differs from what happens during actual cannabis use (which primarily engages CB1). Small sample size. Limited to two behavioral tasks.