Laboratorio de Neurofarmacología, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears (UIB), Palma de Mallorca, Spain.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jul 2;38(1):78-87. doi: 10.1016/j.pnpbp.2011.11.007. Epub 2011 Nov 23.
The endocannabinoid system and CB(1) receptors participate in the control of emotional behavior and mood through a functional coupling with the classic monoaminergic systems. In general, the acute stimulation of CB(1) receptors increases the activity (spontaneous firing rate) of noradrenergic (NE), serotonergic (5-HT) and dopaminergic (DA) neurons as well as the synthesis and/or release of the corresponding neurotransmitter in specific brain regions. Notably, the antagonist/inverse agonist rimonabant (SR141617A) can decrease the basal activity of NE and 5-HT neurons, suggesting a tonic/constitutive regulation of these neuronal systems by endocannabinoids acting at CB(1) receptors. Monoaminergic systems are modulated via CB(1) receptors by direct or indirect effects depending on the localization of this inhibitory receptor, which can be present on monoaminergic neurons themselves and/or inhibitory (GABAergic) and/or excitatory (glutamatergic) regulatory neurons. The repeated stimulation of CB(1) receptors is not associated with the induction of tolerance (receptor desensitization) on the activity of NE, 5-HT and DA neurons, in contrast to chronic agonist effects on neurotransmitter synthesis and/or release in some brain regions. CB(1) receptor desensitization may alter the direct and/or indirect effects of cannabinoid drugs modulating the functionality of monoaminergic systems. The sustained activation of monoaminergic neurons by cannabinoid drugs can also be related to changes in the function of presynaptic inhibitory α(2)-adrenoceptors or 5-HT(1A) receptors (autoreceptors and heteroreceptors), whose sensitivity is downregulated or upregulated upon chronic CB(1) agonist exposure. The functional interactions between endocannabinoids and monoaminergic systems in the brain indicate a potential role for CB(1) receptor signaling in the neurobiology of various psychiatric disorders, including major depression and schizophrenia as the major syndromes.
内源性大麻素系统和 CB(1)受体通过与经典单胺能系统的功能偶联，参与情绪行为和心境的控制。一般来说，CB(1)受体的急性刺激会增加去甲肾上腺素能 (NE)、5-羟色胺能 (5-HT) 和多巴胺能 (DA) 神经元的活性（自发放电率），以及特定脑区相应神经递质的合成和/或释放。值得注意的是，拮抗剂/反向激动剂利莫那班（SR141617A）可以降低 NE 和 5-HT 神经元的基础活性，表明内源性大麻素通过作用于 CB(1)受体对这些神经元系统进行紧张/组成性调节。单胺能系统通过 CB(1)受体进行调制，其作用取决于该抑制性受体的定位，该受体可以存在于单胺能神经元本身，以及抑制性（GABA 能）和/或兴奋性（谷氨酸能）调节神经元上。与一些脑区的神经递质合成和/或释放的慢性激动剂效应相反，CB(1)受体的重复刺激不会导致 NE、5-HT 和 DA 神经元活性的诱导耐受（受体脱敏）。CB(1)受体脱敏可能会改变调节单胺能系统功能的大麻素药物的直接和/或间接作用。大麻素药物对单胺能神经元的持续激活也可能与突触前抑制性 α(2)-肾上腺素能受体或 5-HT(1A)受体（自受体和异受体）功能的变化有关，这些受体的敏感性在慢性 CB(1)激动剂暴露时会下调或上调。大脑中内源性大麻素系统和单胺能系统之间的功能相互作用表明，CB(1)受体信号在各种精神疾病的神经生物学中可能具有潜在作用，包括作为主要综合征的重度抑郁症和精神分裂症。
