Adverse early life experiences, i.e. abusive parenting, during postnatal development, induce long-lasting effects on the stress response systems and behavior. Such changes persist throughout an individual’s life, making him/her vulnerable to suffer psychiatric disorders, including anxiety disorders and drug addiction. Rat pup maternal separation (MS) is a widely used rodent early-life stress model. MS induces changes in the dopamine and endocannabinoid systems in the nucleus accumbens (NAcc) that facilitate alcohol consumption. In this study, our endeavor was to determine if social isolation during adolescence (aSI) was as efficient as MS to facilitate alcohol intake; and moreover, if their combination (MS + aSI) induces even higher alcohol intake and exacerbates anxiety-like behaviors. Also, we evaluated dopamine and endocannabinoid receptors in the NAcc to describe potential changes caused by MS, aSI or both. Wistar rats were reared under 4 different conditions: non-MS + social housing (SH), MS + SH, non-MS + aSI and MS + aSI. Once these rats became adults they were submitted to a voluntary alcohol intake protocol for 10 days. Similar groups of rats with no exposure to alcohol whatsoever, were sacrificed to dissect out the NAcc to analyze the expression of cannabinoid (CB1R and CB2R) and dopamine (D2R and D3R) receptors. Results showed that MS, aSI and MS + aSI increase both CB1R, D2R and D3R expression in the NAcc and also increase alcohol intake and anxiety. These results suggest that early life adverse experiences induce a reprogramming of the brain’s dopamine and endocannabinoid systems which increases subject’s vulnerability to develop anxiety, alcohol abuse and dependence.

在出生后的发育过程中，不良的早期生活经历，即虐待性的养育方式，会对压力反应系统和行为产生长期影响。这种变化贯穿个人的一生，使他/她容易患上精神疾病，包括焦虑症和毒瘾。大鼠幼崽母体分离 (MS) 是一种广泛使用的啮齿动物早期应激模型。MS 诱导伏隔核 (NAcc) 中的多巴胺和内源性大麻素系统发生变化，从而促进饮酒。在这项研究中，我们努力确定青春期的社会隔离 (aSI) 是否与 MS 一样有效促进酒精摄入；此外，如果它们的组合 (MS + aSI) 会导致更高的酒精摄入量并加剧类似焦虑的行为。还，我们评估了 NAcc 中的多巴胺和内源性大麻素受体，以描述由 MS、aSI 或两者引起的潜在变化。Wistar 大鼠在 4 种不同条件下饲养：非 MS + 社会住房 (SH)、MS + SH、非 MS + aSI 和 MS + aSI。一旦这些老鼠长大成人，他们就接受了为期 10 天的自愿饮酒方案。未接触任何酒精的类似大鼠组被处死以解剖出 NAcc 以分析大麻素（CB1R 和 CB2R）和多巴胺（D2R 和 D3R）受体的表达。结果表明，MS、aSI 和 MS + aSI 增加了 NAcc 中 CB1R、D2R 和 D3R 的表达，还增加了酒精摄入量和焦虑。