Autor: |
Xi, Zheng‐Xiong, Muldoon, Pretal, Wang, Xiao‐Fei, Bi, Guo‐Hua, Damaj, M. Imad, Lichtman, Aron H., Pertwee, Roger G., Gardner, Eliot L., Xi, Zheng-Xiong, Wang, Xiao-Fei, Bi, Guo-Hua |
Předmět: |
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Zdroj: |
British Journal of Pharmacology; Dec2019, Vol. 176 Issue 24, p4773-4784, 12p, 3 Charts, 7 Graphs |
Abstrakt: |
Background and Purpose: Both types of cannabinoid receptors-CB1 and CB2 -regulate brain functions relating to addictive drug-induced reward and relapse. CB1 receptor antagonists and CB2 receptor agonists have anti-addiction efficacy, in animal models, against a broad range of addictive drugs. Δ9 -Tetrahydrocannabivarin (Δ9 -THCV)-a cannabis constituent-acts as a CB1 antagonist and a CB2 agonist. Δ8 -Tetrahydrocannabivarin (Δ8 -THCV) is a Δ9 -THCV analogue with similar combined CB1 antagonist/CB2 agonist properties.Experimental Approach: We tested Δ8 -THCV in seven different rodent models relevant to nicotine dependence-nicotine self-administration, cue-triggered nicotine-seeking behaviour following forced abstinence, nicotine-triggered reinstatement of nicotine-seeking behaviour, acquisition of nicotine-induced conditioned place preference, anxiety-like behaviour induced by nicotine withdrawal, somatic withdrawal signs induced by nicotine withdrawal, and hyperalgesia induced by nicotine withdrawal.Key Results: Δ8 -THCV significantly attenuated intravenous nicotine self-administration and both cue-induced and nicotine-induced relapse to nicotine-seeking behaviour in rats. Δ8 -THCV also significantly attenuated nicotine-induced conditioned place preference and nicotine withdrawal in mice.Conclusions and Implications: We conclude that Δ8 -THCV may have therapeutic potential for the treatment of nicotine dependence. We also suggest that tetrahydrocannabivarins should be tested for possible anti-addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans. [ABSTRACT FROM AUTHOR] |
Databáze: |
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