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

The takeaway

Adolescent rats exposed to a CB2 receptor blocker showed slower acquisition of Pavlovian reward learning in adulthood but no change in instrumental conditioning, suggesting CB2 receptors play a selective role in reward system development.

Neuroscience researchers, reward learning specialists, adolescent brain development investigators

Adolescent CB2 blockade impaired Pavlovian but not instrumental reward learning

What the researchers found

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.

Why it matters

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 numbers in context

Adolescent exposure postnatal days 28-41; significantly slower Pavlovian autoshaping acquisition F(2,19)=5.964, p=0.010; no effect on instrumental conditioning

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Novel finding with clear statistical significance, but limited by male-only design and small sample in a single preclinical study.

When this study was published

Published in 2021.

The bigger picture

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.

Questions still open

Would adolescent cannabis use, which primarily acts through CB1 receptors, produce similar selective effects on reward learning? Does the Pavlovian learning deficit translate to increased vulnerability to cue-triggered drug seeking?

Common questions

What is the difference between Pavlovian and instrumental learning?

Pavlovian learning involves associating environmental cues with rewards (like a light predicting food). Instrumental learning involves learning that specific actions produce rewards (like pressing a lever to get food). The study found CB2 receptors during adolescence matter for the first type but not the second.

Why focus on CB2 receptors?

CB2 receptors were long thought to function mainly in the immune system, but recent research has identified their role in the brain's reward pathway. This study adds to evidence that CB2 receptors are important for brain development during adolescence.

Read the original research

Discordant Effects of Cannabinoid 2 Receptor Antagonism/Inverse Agonism During Adolescence on Pavlovian and Instrumental Reward Learning in Adult Male Rats.

Frontiers in synaptic neuroscience, 13, 732402

View on PubMed ↗Publisher’s paper ↗

Citation

Ellner, Danna; Hallam, Bryana; Frie, Jude A; Thorpe, Hayley H A; Shoaib, Muhammad; Kayir, Hakan; Jenkins, Bryan W; Khokhar, Jibran Y. (2021). Discordant Effects of Cannabinoid 2 Receptor Antagonism/Inverse Agonism During Adolescence on Pavlovian and Instrumental Reward Learning in Adult Male Rats.. Frontiers in synaptic neuroscience, 13, 732402. https://doi.org/10.3389/fnsyn.2021.732402