Diana M, Melis M, Gessa G L
Department of Drug Sciences, University of Sassari, Italy.
Eur J Neurosci. 1998 Sep;10(9):2825-30. doi: 10.1111/j.1460-9568.1998.00292.x.
The intravenous administration of the psychoactive constituent of marijuana, delta9-tetrahydrocannabinol (delta9-THC) (62.5-1000 microg/kg), and the synthetic cannabinoid agonist WIN 55212,2 (WIN) (62.5-500 microg/kg), produced a dose-related increase in the firing rate and burst firing in the majority of antidromically identified meso-prefrontal dopaminergic neurons. In a restricted number of neurons (n=4), WIN administration did not increase firing rate but produced an increment of bursting activity. These effects of the cannabinoids were reversed by the intravenous administration of SR 141716 A, a selective cannabinoid antagonist (1 mg/kg), per se ineffective to modify the electrical activity of dopaminergic neurons. The results indicate that stimulation of cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic transmission. Considering that supranormal stimulation of D1 dopamine receptors in the prefrontal cortex has been shown to impair working memory, the present results suggest that the negative effects of cannabinoids on cognitive processes might be related to the activation of dopaminergic transmission in the prefrontal cortex.
静脉注射大麻的精神活性成分Δ9-四氢大麻酚（Δ9-THC）（62.5 - 1000微克/千克）以及合成大麻素激动剂WIN 55212,2（WIN）（62.5 - 500微克/千克），在大多数经逆向鉴定的中脑前额叶多巴胺能神经元中，引发了与剂量相关的放电频率增加和爆发式放电。在数量有限的神经元（n = 4）中，注射WIN并未增加放电频率，但却使爆发活动增加。静脉注射选择性大麻素拮抗剂SR 141716 A（1毫克/千克）可逆转大麻素的这些作用，而该拮抗剂本身对改变多巴胺能神经元的电活动无效。结果表明，大麻素CB1受体的刺激会导致中脑前额叶多巴胺能传递的激活。鉴于前额叶皮质中D1多巴胺受体的超常刺激已被证明会损害工作记忆，目前的结果表明，大麻素对认知过程的负面影响可能与前额叶皮质中多巴胺能传递的激活有关。
