Maternal separation and proclivity for ethanol intake: a potential role of the endocannabinoid system in rats

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.