Pistis M, Porcu G, Melis M, Diana M, Gessa G L
B.B. Brodie Department of Neuroscience, University of Cagliari, via Porcell 4, 09124 Cagliari, Italy.
Eur J Neurosci. 2001 Jul;14(1):96-102. doi: 10.1046/j.0953-816x.2001.01612.x.
Cannabinoids activate the firing of mesoprefrontocortical dopamine neurons and release dopamine in the prefrontal cortex. This study was undertaken with the aim of clarifying the interaction between cannabinoids and mesocortical system in the prefrontal cortex. The effect of Delta9-tetrahydrocannabinol (Delta9-THC) and the synthetic CB1 agonist WIN55,212-2 (WIN) was studied by extracellular single unit recordings, in chloral hydrate anaesthetised rats, on the spontaneous activity of pyramidal neurons and on the inhibition produced on these neurons by the electrical stimulation of the ventral tegmental area (VTA). Intravenously administered Delta9-THC and WIN (1.0 and 0.5 mg/kg, respectively), increased the firing rate of pyramidal neurons projecting to the VTA. VTA stimulation produced a phasic inhibition (167 +/- 6 ms) in 79% of prefrontal cortex pyramidal neurons. Delta9-THC and WIN reverted this inhibition in 73% and 100% of the neurons tested, respectively. The subsequent administration of the selective CB1 antagonist SR141716A (1 mg/kg) readily suppressed the effects of both cannabinoids and restored the inhibitory response to VTA stimulation. Moreover, when administered alone, SR141716A prolonged the inhibition in 55.6% of the neurons tested. The results indicate that stimulation of CB1 receptors by cannabinoids results in an enhanced excitability of prefrontal cortex pyramidal neurons as indexed by the suppression of the inhibitory effect of VTA stimulation and by the increase in firing rate of antidromically identified neurons projecting to the VTA. Furthermore, our results support the view that endogenous cannabinoids exert a negative control on dopamine activity in the prefrontal cortex. This study may be relevant in helping to understand the influence of cannabinoids on cognitive processes mediated by the prefrontal cortex.
大麻素可激活中脑前额叶皮质多巴胺能神经元的放电，并在前额叶皮质释放多巴胺。本研究旨在阐明大麻素与前额叶皮质中脑皮质系统之间的相互作用。通过细胞外单单位记录，在水合氯醛麻醉的大鼠中，研究了Δ9-四氢大麻酚（Δ9-THC）和合成CB1激动剂WIN55,212-2（WIN）对锥体神经元自发活动以及腹侧被盖区（VTA）电刺激对这些神经元产生的抑制作用。静脉注射Δ9-THC和WIN（分别为1.0和0.5mg/kg）可增加投射至VTA的锥体神经元的放电频率。VTA刺激在79%的前额叶皮质锥体神经元中产生了相位性抑制（167±6ms）。Δ9-THC和WIN分别在73%和100%的受试神经元中逆转了这种抑制作用。随后给予选择性CB1拮抗剂SR141716A（1mg/kg）可轻易抑制两种大麻素的作用，并恢复对VTA刺激的抑制反应。此外，单独给药时，SR141716A可使55.6%的受试神经元的抑制作用延长。结果表明，大麻素对CB1受体的刺激导致前额叶皮质锥体神经元兴奋性增强，这表现为VTA刺激抑制作用的抑制以及投射至VTA的逆向鉴定神经元放电频率的增加。此外，我们的结果支持内源性大麻素对前额叶皮质多巴胺活性发挥负性调控作用的观点。本研究可能有助于理解大麻素对由前额叶皮质介导的认知过程的影响。
