Grupo de Neurociencias, Laboratorio de Canabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Neuroscience. 2012 Oct 25;223:296-304. doi: 10.1016/j.neuroscience.2012.07.071. Epub 2012 Aug 10.
Maternal separation (MS) during the first postnatal weeks induces alcohol intake and a reduction in the expression of glucocorticoid receptors (GR). Adults' alcohol consumption may depend on changes in the endocannabinoid system (eCBs). Our goal was to evaluate the status of the eCBs before the exposition to alcohol to support the notion that eCBs' alterations prompt rats to drink alcohol. To reach this goal we subjected rats to MS for the first 2 postnatal weeks. Then, we allowed rats to grow with no further manipulation until they reached adulthood. Thereafter, rats were exposed to an alcohol solution (10% of alcohol in water) as the only source of drinking liquid (forced alcohol ingestion). At the end of this period, tap water was added as an option for drinking liquid (voluntary alcohol ingestion) for another 10 days. Different groups of rats (non-MS, and MS) were sacrificed when adult but with no exposition to alcohol whatsoever, to dissect frontal cortex (FCx), ventral striatum (VS) and hippocampus (HIP) to analyze the following: The expression of cannabinoid receptor 1 (CB1R), CB2R, GR and methylated CpG-binding protein 2 (MeCP2). Levels of GABA and glutamate were quantified in the same brain structures. We found CB1 receptor expression increased in the VS while it was decreased in the FCx in MS subjects. No changes in the CB2R or in the MeCP2 were detected. We found GABA levels increased in FCx and HIP but decreased in VS in MS. Likewise, glutamate levels increased in the FCx but decreased in the HIP in MS subjects. These findings suggest that MS induces changes in the CB1R expression, which might contribute to induce a proclivity to ingest alcohol and, potentially, other drugs.
母体分离（MS）在产后的前几周会导致酒精摄入增加和糖皮质激素受体（GR）表达减少。成年人的酒精摄入量可能取决于内源性大麻素系统（eCBs）的变化。我们的目标是评估暴露于酒精之前的 eCBs 状态，以支持 eCBs 的改变促使大鼠饮酒的观点。为了达到这个目标，我们让大鼠在出生后的前 2 周接受 MS。然后，我们让大鼠在没有进一步操作的情况下生长，直到它们成年。此后，大鼠被暴露于酒精溶液（水中 10%的酒精）作为唯一的饮用液体来源（强制饮酒）。在这段时间结束时，加入自来水作为饮用液体的选择（自愿饮酒），持续 10 天。不同组的大鼠（非 MS 和 MS）在成年后但没有接触过酒精的情况下被处死，以解剖前额皮质（FCx）、腹侧纹状体（VS）和海马（HIP），分析以下内容：大麻素受体 1（CB1R）、CB2R、GR 和甲基化 CpG 结合蛋白 2（MeCP2）的表达。在相同的脑结构中定量了 GABA 和谷氨酸的水平。我们发现 MS 组 VS 中的 CB1 受体表达增加，而 FCx 中的 CB1 受体表达减少。未检测到 CB2R 或 MeCP2 的变化。我们发现 MS 组 FCx 和 HIP 中的 GABA 水平增加，而 VS 中的 GABA 水平降低。同样，MS 组 FCx 中的谷氨酸水平增加，而 HIP 中的谷氨酸水平降低。这些发现表明 MS 诱导 CB1R 表达的变化，这可能有助于诱导摄入酒精和潜在其他药物的倾向。
