Scherma Maria, Muntoni Anna Lisa, Melis Miriam, Fattore Liana, Fadda Paola, Fratta Walter, Pistis Marco
Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cittadella Universitaria, Monserrato (CA), 09042, Italy.
Neuroscience Institute, section of Cagliari, National Research Council, Cagliari, Italy.
Psychopharmacology (Berl). 2016 May;233(10):1765-77. doi: 10.1007/s00213-015-4196-3. Epub 2016 Jan 4.
Several lines of evidence suggest that endocannabinoid and nicotinic cholinergic systems are implicated in the regulation of different physiological processes, including reward, and in the neuropathological mechanisms of psychiatric diseases, such as addiction. A crosstalk between these two systems is substantiated by the overlapping distribution of cannabinoid and nicotinic acetylcholine receptors in many brain structures.
We will review recent preclinical data showing how the endocannabinoid and nicotinic cholinergic systems interact bidirectionally at the level of the brain reward pathways, and how this interaction plays a key role in modulating nicotine and cannabinoid intake and dependence.
Many behavioral and neurochemical effects of nicotine that are related to its addictive potential are reduced by pharmacological blockade or genetic deletion of type-1 cannabinoid receptors, inhibition of endocannabinoid uptake or metabolic degradation, and activation of peroxisome proliferator-activated-receptor-α. On the other hand, cholinergic antagonists at α7 nicotinic acetylcholine receptors as well as endogenous negative allosteric modulators of these receptors are effective in blocking dependence-related effects of cannabinoids.
Pharmacological manipulation of the endocannabinoid system and endocannabinoid-like neuromodulators shows promise in the treatment of nicotine dependence and in relapse prevention. Likewise, drugs acting at nicotinic acetylcholine receptors might prove useful in the therapy of cannabinoid dependence. Research by Steven R. Goldberg has significantly contributed to the progress in this research field.
多项证据表明，内源性大麻素系统和烟碱型胆碱能系统参与调控包括奖赏在内的多种生理过程，以及成瘾等精神疾病的神经病理机制。大麻素受体和烟碱型乙酰胆碱受体在许多脑结构中的分布重叠，证实了这两个系统之间存在相互作用。
我们将综述近期临床前数据，这些数据展示了内源性大麻素系统和烟碱型胆碱能系统如何在脑奖赏通路水平上双向相互作用，以及这种相互作用如何在调节尼古丁和大麻素的摄入及依赖方面发挥关键作用。
通过对1型大麻素受体进行药理阻断或基因敲除、抑制内源性大麻素摄取或代谢降解以及激活过氧化物酶体增殖物激活受体-α，可降低尼古丁许多与其成瘾潜力相关的行为和神经化学效应。另一方面，α7烟碱型乙酰胆碱受体的胆碱能拮抗剂以及这些受体的内源性负变构调节剂可有效阻断大麻素的依赖相关效应。
对内源性大麻素系统和类内源性大麻素神经调节剂进行药理操作，在治疗尼古丁依赖和预防复发方面显示出前景。同样，作用于烟碱型乙酰胆碱受体的药物可能对大麻素依赖治疗有用。史蒂文·R·戈德堡的研究对该研究领域的进展做出了重大贡献。
