CB 1 positive allosteric modulation attenuates Δ 9 -THC withdrawal and NSAID-induced gastric inflammation.

Autor: Trexler KR; Department of Psychology, West Virginia University, Morgantown, WV, USA., Eckard ML; Department of Psychology, West Virginia University, Morgantown, WV, USA., Kinsey SG; Department of Psychology, West Virginia University, Morgantown, WV, USA; Department of Neuroscience, West Virginia University, Morgantown, WV, USA. Electronic address: steven.kinsey@mail.wvu.edu.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2019 Feb; Vol. 177, pp. 27-33. Date of Electronic Publication: 2018 Dec 28.
DOI: 10.1016/j.pbb.2018.12.009
Abstrakt: Recently, multiple compounds have been synthesized that target the allosteric binding site(s) of CB 1. These CB 1 positive allosteric modulators may capture the benefits of cannabinoid receptor activation without unwanted psychoactive effects, such as sedation. For example, ZCZ011 blocks neuropathic pain, absent the catalepsy, sedation, and hypothermia caused by CB 1 orthosteric modulators, including Δ 9 -tetrahydrocannabinol (THC). The primary goal of the present study was to evaluate the potential of ZCZ011 to attenuate somatic signs of cannabinoid withdrawal in mice. Mice were repeatedly administered THC (10 mg/kg, s.c.) or vehicle, and withdrawal was either precipitated using the CB 1 antagonist rimonabant (3 mg/kg, i.p.) or elicited spontaneously via THC abstinence. ZCZ011 (≥10 mg/kg, i.p.) significantly attenuated somatic signs of withdrawal, including head twitches and paw tremors, but had no effect on locomotor activity or conditioned place preference. We next tested the antiulcerogenic properties of CB 1 positive allosteric modulation. Mice were fasted for 22 h, administered ZCZ011, and gastric hemorrhages were induced with the nonsteroidal anti-inflammatory drug diclofenac sodium (100 mg/kg, p.o.). ZCZ011 alone had no effect on gastric ulceration, but ZCZ011 (≥10 mg/kg) blocked ulcer formation when combined with a subthreshold MAGL inhibitor (JZL184; 1 mg/kg, i.p.). Thus, CB 1 positive allosteric modulation is a novel approach to treat cannabinoid dependence and gastric inflammation.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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