Muntoni Anna Lisa, Pillolla Giuliano, Melis Miriam, Perra Simona, Gessa Gian Luigi, Pistis Marco
Institute of Neuroscience C.N.R., c/o University of Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
Eur J Neurosci. 2006 May;23(9):2385-94. doi: 10.1111/j.1460-9568.2006.04759.x.
The noradrenergic pathway arising from the locus coeruleus (LC) is involved in the regulation of attention, arousal, cognitive processes and sleep. These physiological activities are affected by Cannabis exposure - both in humans and laboratory animals. In addition, exogenous cannabinoids, as well as pharmacological and genetic manipulation of the endocannabinoid system, are known to influence emotional states (e.g. anxiety) for which a contributory role of the LC-noradrenergic system has long been postulated. However, whether cannabinoid administration would affect the LC neuronal activity in vivo is still unknown. To this end, single-unit extracellular recordings were performed from LC noradrenergic cells in anaesthetized rats. Intravenous injection of both the synthetic cannabinoid agonist, WIN55212-2, and the main psychoactive principle of Cannabis, Delta9-tetrahydrocannabinol, dose-dependently increased the firing rate of LC noradrenergic neurons, with WIN55212-2 being the most efficacious. Similar results were obtained by the administration of these drugs into a lateral ventricle. Cannabinoid-induced stimulation of LC noradrenergic neuronal activity was counteracted by SR141716A, a cannabinoid receptor antagonist/reverse agonist, which by itself slightly reduced LC discharge rate. Moreover, WIN55212-2 suppressed the inhibition of noradrenergic cells produced by stimulation of the major gamma-aminobutyric acid (GABA)ergic afferent to the LC, the nucleus prepositus hypoglossi. Altogether, these findings suggest the involvement of noradrenergic pathways in some consequences of Cannabis intake (e.g. cognitive and attention deficits, anxiety reactions), as well as a role for cannabinoid receptors in basic brain activities sustaining arousal and emotional states.
源自蓝斑（LC）的去甲肾上腺素能通路参与注意力、觉醒、认知过程及睡眠的调节。这些生理活动会受到大麻暴露的影响——无论是在人类还是实验动物中。此外，外源性大麻素以及内源性大麻素系统的药理学和基因操作，已知会影响情绪状态（如焦虑），长期以来一直假定LC-去甲肾上腺素能系统在其中起作用。然而，大麻素给药是否会在体内影响LC神经元活动仍不清楚。为此，在麻醉大鼠的LC去甲肾上腺素能细胞上进行了单单位细胞外记录。静脉注射合成大麻素激动剂WIN55212-2以及大麻的主要精神活性成分Δ9-四氢大麻酚，均剂量依赖性地增加了LC去甲肾上腺素能神经元的放电频率，其中WIN55212-2最为有效。将这些药物注入侧脑室也得到了类似结果。大麻素诱导的LC去甲肾上腺素能神经元活动刺激被大麻素受体拮抗剂/反向激动剂SR141716A抵消，SR141716A本身会轻微降低LC放电频率。此外，WIN55212-2抑制了刺激LC主要γ-氨基丁酸（GABA）能传入神经——舌下前置核所产生的去甲肾上腺素能细胞的抑制作用。总之，这些发现表明去甲肾上腺素能通路参与了大麻摄入的某些后果（如认知和注意力缺陷、焦虑反应），以及大麻素受体在维持觉醒和情绪状态的基本脑活动中的作用。
