ArticleBehavioral and brain functions : BBF2025
Cannabinoid type 1 receptors in the mice prefrontal cortex regulate object location memory acquisition via GABAergic neurons.
Article in Behavioral and brain functions : BBF, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAdverse psychiatric symptoms caused by cannabis are a significant concern, and Δ9-tetrahydrocannabinol (THC) has been identified as a key contributor to these symptoms. THC binds to cannabinoid type 1 receptors (CB1Rs), which are abundant in the brain and associated with cognition. The prefrontal cortex (PFC) is crucial for cognitive functions. However, the functions of CB1Rs in the PFC in cognition processes remain unclear. Here, we injected arachidonylcyclopropylamide (ACPA), a CB1Rs agonist, into the PFC of male C57BL/6J mice via the cannula and conducted cognitive tests, including the novel object recognition test and object location test (OLT).
resultsThese tests assessed memory in three stages: acquisition, consolidation, and retrieval. ACPA was administered immediately before each stage, and its intra-PFC administration specifically impaired memory acquisition in the OLT. In addition, in vivo microdialysis revealed that ACPA reduced extracellular GABA levels within the PFC. Next, we produced an adeno-associated virus with a glutamic acid decarboxylase promoter and an hM3Dq-encording chemogenic activator to activate GABAergic neurons in the PFC. Subsequently, deschloroclozapine (DCZ), an hM3Dq agonist, restored the memory acquisition impaired by ACPA.
conclusionOur findings suggest that CB1Rs in the PFC are involved in memory acquisition through the regulation of GABA release, offering new insights into how cannabis use lead to cognitive impairment.
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