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

The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannab...

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Bibliographic Details
Main Authors: Danna Ellner, Bryana Hallam, Jude A. Frie, Hayley H. A. Thorpe, Muhammad Shoaib, Hakan Kayir, Bryan W. Jenkins, Jibran Y. Khokhar
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Synaptic Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnsyn.2021.732402/full
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Summary:The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannabinoid receptor type 2 (CB2R) was initially thought to predominantly function in the peripheral nervous system, but more recent studies have implicated its role in the mesolimbic pathway, a network largely attributed to reward circuitry and reward motivated behavior, which undergoes extensive changes during adolescence. It is therefore important to understand how CB2R modulation during adolescence can impact reward-related behaviors in adulthood. In this study, adolescent male rats (postnatal days 28–41) were exposed to a low or high dose of the CB2R antagonist/inverse agonist SR144528 and Pavlovian autoshaping and instrumental conditional behavioral outcomes were measured in adulthood. SR144528-treated rats had significantly slower acquisition of the autoshaping task, seen by less lever pressing behavior over time [F(2, 19) = 5.964, p = 0.010]. Conversely, there was no effect of adolescent SR144528 exposure on instrumental conditioning. These results suggest that modulation of the CB2R in adolescence differentially impacts reward-learning behaviors in adulthood.
ISSN:1663-3563