Pertwee R G, Browne S E, Ross T M, Stretton C D
Division of Pharmacology, School of Biomedical Sciences, Marischal College University of Aberdeen, Scotland.
Pharmacol Biochem Behav. 1991 Nov;40(3):581-5. doi: 10.1016/0091-3057(91)90366-a.
Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.
用小鼠进行了实验，以确定已知可增强δ-9-四氢大麻酚（THC）诱导的僵住症的苯二氮卓类药物氟西泮或GABA摄取抑制剂NO-328的剂量，是否也会在产生某些其他效应时与THC产生协同作用。在抗伤害感受（甩尾试验）的产生中，或者在一项比较有或没有THC或大麻二酚存在时氟西泮延迟静脉注射戊四氮诱导的阵挛性惊厥发作能力的试验中，均未检测到协同作用。THC的体温过低效应不受NO-328影响，但氟西泮可增强该效应，尽管仅在高于增强THC诱导的僵住症所需的剂量时才会如此。用豚鼠回肠进行的体外实验表明，THC抑制电诱发收缩的能力不受GABA（B）受体拮抗剂δ-氨基-n-戊酸的影响，并且对GABA产生耐受性的制剂对THC的反应正常。在未刺激的回肠纵肌中，GABA诱导的收缩会被THC减弱。我们得出结论，从我们的数据中几乎没有证据表明所研究的任何THC效应是由GABA介导的。
