Carta G, Nava F, Gessa G L
Guy M. Everett Laboratory of Neuropsychopharmacology, Department of Neuroscience 'Bernard B. Brodie', University of Cagliari, Via Porcell 4, 09124, Cagliari, Italy.
Brain Res. 1998 Oct 26;809(1):1-4. doi: 10.1016/s0006-8993(98)00738-0.
The effects of acute and repeated administration of Delta9-tetrahydrocannabinol (Delta9-THC), the psychoactive principle of marijuana, on acetylcholine release in the hippocampus was studied in freely moving rats by microdialysis. The acute intraperitoneal (i.p.) administration of Delta9-THC at the doses of 2.5 and 5 mg/kg reduced acetylcholine release by about 25% and 45%, respectively. A dose of 7.5 mg/kg produced no further reduction. Delta9-THC effects were antagonized by the cannabinoid CB1 antagonist SR141716A at the i.p. dose of 1 mg/kg, per se ineffective in modifying acetylcholine concentrations. After a repeated exposure (twice daily for up to seven days) to Delta9-THC (7.5 mg/kg, i.p.) or vehicle (0.3 ml/kg, i.p.), the inhibitory effect of Delta9-THC (2.5 and 5 mg/kg, i.p) on acetylcholine release was not reduced. The results confirm previous observations that cannabinoids inhibit acetylcholine release through cannabinoid CB1 receptors, and indicate that no tolerance to this effects develops after a repeated Delta9-THC administration.
通过微透析技术，在自由活动的大鼠中研究了大麻的精神活性成分Δ9-四氢大麻酚（Δ9-THC）急性和重复给药对海马中乙酰胆碱释放的影响。腹腔注射2.5和5mg/kg剂量的Δ9-THC可分别使乙酰胆碱释放减少约25%和45%。7.5mg/kg的剂量未进一步降低释放量。腹腔注射1mg/kg的大麻素CB1拮抗剂SR141716A可拮抗Δ9-THC的作用，该拮抗剂本身对改变乙酰胆碱浓度无效。在对Δ9-THC（7.5mg/kg，腹腔注射）或溶剂（0.3ml/kg，腹腔注射）进行重复暴露（每天两次，持续七天）后，Δ9-THC（2.5和5mg/kg，腹腔注射）对乙酰胆碱释放的抑制作用并未减弱。结果证实了先前的观察结果，即大麻素通过大麻素CB1受体抑制乙酰胆碱释放，并表明重复给予Δ9-THC后不会产生对该作用的耐受性。
