Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats.

Autor:	Nedelescu H; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Wagner GE; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., De Ness GL; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Carroll A; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Kerr TM; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Wang J; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Zhang S; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Chang S; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Than AH; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Emerson NE; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Suto N; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California., Weiss F; Department of Neuroscience (HN, GEW, GLD, AC, TMK, JW, SZ, SC, AHT, NEE, NS, FW), The Scripps Research Institute, La Jolla, California.
Jazyk:	angličtina
Zdroj:	Biological psychiatry global open science [Biol Psychiatry Glob Open Sci] 2022 Jan; Vol. 2 (1), pp. 70-78. Date of Electronic Publication: 2021 Jul 07.
DOI:	10.1016/j.bpsgos.2021.06.014
Abstrakt:	Background: Cannabidiol (CBD) has received attention for the treatment of substance use disorders. In preclinical models of relapse, CBD attenuates drug seeking across several drugs of abuse, including cocaine. However, in these models CBD has not been consistently effective. This inconsistency in CBD effects may be related to presently insufficient information on the full spectrum of CBD dose effects on drug-related behaviors. Methods: We address this issue by establishing a full dose-response profile of CBD's actions using expression of cocaine-induced conditioned place preference as a model for drug-motivated behavior in male rats and by concurrently identifying dose-dependent effects of CBD on underlying neuronal activation and distinct neuronal phenotypes showing dose-dependent activation changes. Additionally, we established CBD levels in plasma and brain samples. Results: CBD produced linear increases in CBD brain/plasma concentrations but suppressed conditioned place preference in a distinct U-shaped manner. In parallel with its behavioral effects, CBD produced U-shaped suppressant effects on neuronal activation in the prelimbic but not infralimbic cortex or nucleus accumbens core and shell. RNAscope in situ hybridization identified suppression of glutamatergic and GABAergic (gamma-aminobutyric acidergic) signaling in the prelimbic cortex as a possible cellular mechanism for the attenuation of cocaine-induced conditioned place preference by CBD. Conclusions: The findings extend previous evidence on the potential of CBD in preventing drug-motivated behavior. However, CBD's dose-response profile may have important dosing implications for future clinical applications and may contribute to the understanding of discrepant CBD effects on drug seeking reported in the literature. Competing Interests: The authors report no biomedical financial interests or potential conflicts of interest.
Databáze:	MEDLINE
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