Gabapentin attenuates somatic signs of precipitated THC withdrawal in mice.

Autor: Eckard ML; Department of Environmental Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA; Department of Psychology, West Virginia University, Morgantown, WV, USA., Kinsey SG; Department of Psychology, West Virginia University, Morgantown, WV, USA; School of Nursing, University of Connecticut, Storrs, CT, USA. Electronic address: steven.kinsey@uconn.edu.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2021 Jun 01; Vol. 190, pp. 108554. Date of Electronic Publication: 2021 Apr 15.
DOI: 10.1016/j.neuropharm.2021.108554
Abstrakt: Cannabis is the most frequently used federally illicit substance in the United States. However, there are currently no FDA-approved pharmacotherapies to mitigate the withdrawal symptoms associated with cessation in heavy users. A promising, readily available, non-cannabinoid therapy are the gabapentinoids. Although currently approved for epilepsy and neuropathic pain, gabapentinoids are increasingly used for their "off-label" efficacy in treating various psychiatric conditions and substance abuse. Gabapentin (GBP) synergizes with cannabinoid agonism in neuropathic pain models, substitutes for Δ 9 -tetrahydrocannabinol (THC) in drug discrimination procedures, and reduced withdrawal symptoms in an outpatient clinical trial. However, there are limited data on the biological plausibility of the therapeutic action of gabapentinoids in cannabinoid withdrawal in preclinical models. The purpose of the current study was to determine the efficacy of GBP on attenuating THC withdrawal in mice, using an array of tests targeting withdrawal-induced and withdrawal-suppressed behaviors. Separate cohorts of male and female mice were administered THC (10 mg/kg, s.c.) or vehicle for 5.5 days, and withdrawal was precipitated by the CB 1 antagonist rimonabant (2 or 3 mg/kg, i.p.) on the sixth day. GBP (≥10 mg/kg) reduced somatic signs of withdrawal (i.e., paw tremors and head twitches), but had no effect in locomotor activity or conditioned place preference. GBP (50 mg/kg) also restored withdrawal-suppressed responding on a progressive ratio reinforcement schedule. However, GBP (50 mg/kg) had no effect in withdrawal-suppressed marble burying or tail suspension struggling and did not normalize the stress response induced by THC withdrawal, as indicated by plasma corticosterone. These data suggest gabapentin may be effective at treating cannabinoid withdrawal symptoms including somatic and affective symptoms but may act independently of endocrine stress activation.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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