Prefrontal cortical distribution of muscarinic M2 and cannabinoid-1 (CB1) receptors in adult male mice with or without chronic adolescent exposure to Δ9-tetrahydrocannabinol.
Miguel Garzón, June Chan, Ken Mackie, Virginia M Pickel
Cerebral Cortex November 21, 2022 DOI: 10.1093/cercor/bhac024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult C57BL/6 J male mice that received vehicle or escalating-dose Δ9-THC during adolescence |
| Dose | escalating dose |
| Measures | electron microscopic dual CB1R and M2R immunolabeling, M2R-immunogold density |
| Topics | Cannabis |
| Keywords | Cannabinoid Cholinergic Prelimbic Ultrastructure |
| Key findings | Adolescent Δ9-THC treatment increased plasmalemmal M2R-immunogold density specifically in large dendrites receiving input from CB1R-labeled terminals and decreased cytoplasmic M2R-immunogold density in small spines of the prelimbic prefrontal cortex. The authors conclude that Δ9-THC engagement of CB1Rs during adolescence increases M2R surface accumulation in large proximal dendrites and decreases M2R cytoplasmic expression in small spines. |
Abstract
Chronic adolescent administration of marijuana's major psychoactive compound, ∆9-tetrahydrocannabinol (Δ9-THC), produces adaptive changes in adult social and cognitive functions sustained by prelimbic prefrontal cortex (PL-PFC). Memory and learning processes in PL-PFC neurons can be regulated through cholinergic muscarinic-2 receptors (M2R) and modulated by activation of cannabinoid-1 receptors (CB1Rs) targeted by Δ9-THC. Thus, chronic exposure to Δ9-THC during adolescence may alter the expression and/or distribution of M2Rs in PL-PFC neurons receiving CB1R terminals. We tested this hypothesis by using electron microscopic dual CB1R and M2R immunolabeling in adult C57BL/6 J male mice that had received vehicle or escalating dose of Δ9-THC through adolescence. In vehicle controls, CB1R immunolabeling was mainly localized to axonal profiles virtually devoid of M2R but often apposing M2R-immunoreactive dendrites and dendritic spines. The dendrites received inputs from CB1R-labeled or unlabeled terminals, whereas spines received asymmetric synapses exclusively from axon terminals lacking CB1Rs. Adolescent Δ9-THC significantly increased plasmalemmal M2R-immunogold density exclusively in large dendrites receiving input from CB1R-labeled terminals. In contrast, cytoplasmic M2R-immunogold density decreased in small spines of the Δ9-THC-treated adult mice. We conclude that Δ9-THC engagement of CB1Rs during adolescence increases M2R plasmalemmal accumulation in large proximal dendrites and decreases M2R cytoplasmic expression in small spines of PL-PFC.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 7
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- Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex. Neurobiology of Disease 2015
- delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory. Psychopharmacology October 2011
and 2 more in the library