Prefrontal cortical distribution of muscarinic M2 and cannabinoid-1 (CB1) receptors in adult male mice with or without chronic adolescent exposure to Δ9-tetrahydrocannabinol.


Journal

Cerebral cortex (New York, N.Y. : 1991)
ISSN: 1460-2199
Titre abrégé: Cereb Cortex
Pays: United States
ID NLM: 9110718

Informations de publication

Date de publication:
21 11 2022
Historique:
received: 05 08 2021
revised: 05 01 2022
accepted: 06 01 2022
pubmed: 13 2 2022
medline: 3 12 2022
entrez: 12 2 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35151230
pii: 6527551
doi: 10.1093/cercor/bhac024
pmc: PMC9712711
doi:

Substances chimiques

Dronabinol 7J8897W37S
Receptor, Cannabinoid, CB1 0
Receptor, Muscarinic M2 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

5420-5437

Subventions

Organisme : NIDA NIH HHS
ID : R01 DA042943
Pays : United States
Organisme : NIDA NIH HHS
ID : DA043982
Pays : United States

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Miguel Garzón (M)

Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina UAM, 28029 Madrid, Spain.
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, USA.

June Chan (J)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, USA.

Ken Mackie (K)

Linda and Jack Gill Center for Biomolecular Science, Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.

Virginia M Pickel (VM)

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, USA.

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