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Δ9 -Tetrahydrocannabinol self-administration induces cell type-specific adaptations in the nucleus accumbens core. Addict Biol 2023 Aug;28(8):e13286

Date

07/28/2023

Pubmed ID

37500492

Pubmed Central ID

PMC10924663

DOI

10.1111/adb.13286

Scopus ID

2-s2.0-85165505517 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Drugs of abuse induce cell type-specific adaptations in D1- and D2-medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore) that can bias signalling towards D1-MSNs and enhance relapse vulnerability. Whether Δ9 -tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to self-administer THC + cannabidiol (THC + CBD). After extinction training spine morphology, glutamate transmission, CB1R function and cFOS expression were quantified. We found that extinction from THC + CBD induced a loss of large spine heads in D1- but not D2-MSNs and commensurate reductions in glutamate synaptic transmission. Also, presynaptic CB1R function was impaired selectively at glutamatergic synapses on D1-MSNs, which augmented the capacity to potentiate glutamate transmission. Using cFOS expression as an activity marker, we found no change after extinction but increased cFOS expression in D1-MSNs after cue-induced drug seeking. Contrasting D1-MSNs, CB1R function and glutamate synaptic transmission on D2-MSN synapses were unaffected by THC + CBD use. However, cFOS expression was decreased in D2-MSNs of THC + CBD-extinguished rats and was restored after drug seeking. Thus, CB1R adaptations in D1-MSNs partially predicted neuronal activity changes, posing pathway specific modulation of eCB signalling in D1-MSNs as a potential treatment avenue for cannabis use disorder (CUD).

Author List

Garcia-Keller C, Hohmeister M, Seidling K, Beloate L, Chioma V, Spencer S, Kalivas P, Neuhofer D

Author

Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Dronabinol
Glutamates
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons
Nucleus Accumbens
Rats
Rats, Transgenic
Receptors, Dopamine D1
Synaptic Transmission