Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, Bs As, Argentina; CONICET- Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencia (IBCN), Bs As, Argentina.
CONICET- Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencia (IBCN), Bs As, Argentina.
Neuropharmacology. 2018 Jul 15;137:268-274. doi: 10.1016/j.neuropharm.2018.05.018. Epub 2018 May 25.
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence. In addition, cannabinoid receptor 2 has been found expressed also in the central nervous system at postsynaptic level. In order to analyze the participation of the eCB system on ethanol (EtOH) preference, mice were exposed to cannabinoid agonist WIN 55,212-2 (WIN) for 5 consecutive days during early adolescence. Anxiety tests were performed the day after WIN treatment withdrawal, and EtOH preference was measured throughout adolescence. Mice exposed to WIN during early adolescence exhibited a significant increase in EtOH intake and preference after treatment. Moreover, WIN exposure during early adolescence induced an anxiogenic effect. Morphometric analysis revealed higher dendritic ramifications and fewer dendritic spines in neurons of the substantia nigra pars compacta in WIN-treated mice. On the other hand, immunohistochemical analysis revealed an increase in the number of tryptophan hydroxylase-expressing neurons in the dorsal raphe nucleus but no differences were found in the ventral tegmental area or substantia nigra pars compacta for tyrosine hydroxylase-expressing neurons. These results demonstrate that exposure to WIN in early adolescence can affect neural development and induce alcohol preference and anxiety-like behavior during late adolescence.
内源性大麻素（eCB）系统参与奖励系统的调节，并参与包括酒精在内的不同滥用药物的强化作用。中枢神经系统中 eCB 系统最丰富的受体是 CB1 受体（CB1R），它主要表达在与成瘾相关的区域，如伏隔核、腹侧被盖区、黑质和中缝核。CB1R 在发育早期表达，并在青春期早期达到最高水平。此外，在后突触水平也发现了大麻素受体 2 在中枢神经系统中的表达。为了分析内源性大麻素系统对乙醇（EtOH）偏好的参与，在青春期早期，将小鼠连续 5 天暴露于大麻素激动剂 WIN 55,212-2（WIN）中。WIN 处理后一天进行焦虑测试，并在整个青春期测量 EtOH 偏好。在青春期早期暴露于 WIN 的小鼠在治疗后表现出乙醇摄入量和偏好的显著增加。此外，青春期早期暴露于 WIN 会引起焦虑样效应。形态计量分析显示，WIN 处理小鼠的黑质致密部神经元的树突分支增多，树突棘减少。另一方面，免疫组织化学分析显示，中缝背核表达色氨酸羟化酶的神经元数量增加，但腹侧被盖区或黑质致密部表达酪氨酸羟化酶的神经元没有差异。这些结果表明，青春期早期暴露于 WIN 可影响神经发育，并在青春期后期引起酒精偏好和焦虑样行为。
