CB1 receptors in the brain's reward center are needed to learn that relief feels good | Research

The takeaway

Blocking CB1 cannabinoid receptors in the nucleus accumbens prevented rats from learning to associate a cue with relief from an unpleasant event, but did not affect recall of previously learned relief associations.

Read this if you want to understand how the brain's cannabinoid system helps process relief and emotional learning.

CB1 blockade in the reward center prevented learning that relief is rewarding

What the researchers found

When the CB1 receptor blocker rimonabant was injected directly into the nucleus accumbens before conditioning, rats failed to learn relief associations. A cue paired with the offset of a mildly aversive stimulus normally produces relief learning, where the cue later reduces startle responses. CB1 blockade during learning eliminated this effect.

However, when rimonabant was injected before a retention test (after learning had already occurred without drug treatment), relief memory was unaffected. This dissociation indicates that CB1 receptors in the nucleus accumbens are specifically required for the neural plasticity that forms relief memories, not for retrieving or expressing them.

Why it matters

Relief learning is a fundamental process: the brain learns that the end of something unpleasant is rewarding. This study shows that cannabinoid signaling in the nucleus accumbens is essential for forming these relief memories. This has implications for understanding how cannabis might affect emotional learning and why the endocannabinoid system is involved in processing relief and reward.

The numbers in context

CB1 blockade before conditioning: relief learning was inhibited. CB1 blockade before retention test: no effect on previously learned relief. Drug used: SR141716A (rimonabant) injected directly into nucleus accumbens.

How the study worked

Rats received direct injections of the CB1 antagonist/inverse agonist SR141716A (rimonabant) into the nucleus accumbens at different timepoints during a relief conditioning paradigm. Relief learning was measured by the attenuation of acoustic startle responses to a cue previously paired with relief from a mild foot shock.

What this study cannot tell us

Animal study using direct brain injections, which is not applicable to human drug delivery. Only one brain region was tested. The study used a synthetic CB1 blocker rather than manipulating endocannabinoid levels directly. Relief learning in rats may not fully model human emotional processing.

How to read the evidence

Animal study using targeted brain injections in rats. Provides precise mechanistic data but is far from human application.

When this study was published

Published in 2017. Research on endocannabinoid involvement in emotional and associative learning continues.

The bigger picture

The endocannabinoid system does not just process pleasure; it helps the brain learn that bad things have ended. This relief learning mechanism could be relevant to understanding PTSD, anxiety disorders, and why cannabis users sometimes report that cannabis helps with emotional processing after stressful events.

Questions still open

Does cannabis use enhance or impair relief learning in humans? Could endocannabinoid system dysfunction explain difficulties with emotional processing in PTSD? Are other brain regions also involved in cannabinoid-dependent relief learning?

Common questions

What is relief learning?

Relief learning is when the brain associates an environmental cue with the feeling of relief after something unpleasant ends. For example, hearing a specific tone right after a mild shock stops can make that tone calming in the future. This is a basic form of emotional memory.

Does this mean cannabis affects how we process relief?

The study shows that cannabinoid receptors in the reward center are needed for forming relief memories in rats. Whether cannabis use enhances or disrupts this process in humans is not yet known, but it suggests the endocannabinoid system plays a fundamental role in emotional learning.

Read the original research

Intra-accumbal blockade of endocannabinoid CB1 receptors impairs learning but not retention of conditioned relief.

Neurobiology of learning and memory, 144, 48-52

View on PubMed ↗Publisher’s paper ↗

Citation

Bergado Acosta, Jorge R; Schneider, Miriam; Fendt, Markus. (2017). Intra-accumbal blockade of endocannabinoid CB1 receptors impairs learning but not retention of conditioned relief.. Neurobiology of learning and memory, 144, 48-52. https://doi.org/10.1016/j.nlm.2017.06.001