大麻素CB(1)受体拮抗剂SR141716A在Δ⁹-四氢大麻酚戒断后的作用。
Effects of the cannabinoid CB(1) receptor antagonist, SR141716A, after Delta(9)-tetrahydrocannabinol withdrawal.
作者信息
Beardsley P M, Martin B R
机构信息
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Box 980613, 410 N. 12th Street, Smith Building #756A, Richmond, VA 23298-0613, USA.
出版信息
Eur J Pharmacol. 2000 Jan 3;387(1):47-53. doi: 10.1016/s0014-2999(99)00792-x.
Rats were trained to lever press according to variable interval 10 s schedules during daily experimental sessions composed of six 3 min food reinforcement periods and were treated twice daily for 6 days with either vehicle or escalating regimens of Delta(9)-tetrahydrocannabinol. On days 7 and 8, the rats were challenged with vehicle and cumulative doses of SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4, -dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide hydrochloride), a cannabinoid CB(1) receptor antagonist, up to 3 and 9 mg/kg, respectively. Response rates increased during Delta(9)-tetrahydrocannabinol withdrawal and towards those of the vehicle treatment group suggesting a waning of the direct effects of Delta(9)-tetrahydrocannabinol. SR141716A reduced response rates but only in rats pre-treated with Delta(9)-tetrahydrocannabinol. These data suggest that dependence upon Delta(9)-tetrahydrocannabinol was induced and SR141716A precipitated withdrawal.
在由六个3分钟食物强化期组成的每日实验环节中，训练大鼠按照可变间隔10秒的时间表按压杠杆，并在6天内每天用赋形剂或递增剂量的Δ⁹-四氢大麻酚治疗两次。在第7天和第8天，分别用赋形剂和累积剂量高达3和9 mg/kg的SR141716A（N-（哌啶-1-基）-5-（4-氯苯基）-1-（2,4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺盐酸盐）对大鼠进行激发试验，SR141716A是一种大麻素CB₁受体拮抗剂。在Δ⁹-四氢大麻酚戒断期间，反应率增加，并趋向于赋形剂治疗组的反应率，这表明Δ⁹-四氢大麻酚的直接作用在减弱。SR141716A降低了反应率，但仅在预先用Δ⁹-四氢大麻酚治疗的大鼠中出现这种情况。这些数据表明，诱导了对Δ⁹-四氢大麻酚的依赖性，并且SR¹⁴¹⁷¹⁶A引发了戒断反应。
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