Neonatal Maternal Separation and Alcohol Abuse in C57BL/6J mice: A Study of the Functional Alterations of GABAergic and GLUergic Systems and the Possible Protective Role of Esterogen

Stress in early life may play a very important role in neurobiology of addiction developed in adulthood. In this study we investigated the effects of neonatal repeated maternal separation (RMS) on alcohol abuse in adult C57BL/6J mice and potential functional alterations of GABAergic and GLUergic systems in different brain areas. Male animals subjected to RMS consumed significantly higher amount of ethanol when compared to control counterparts. In addition, RMS is markedly associated with severe impairments in both GABAergic and GLUergic transmission that are crucial to the physiologic function of brain areas such as hippocampus and amygdala, involving learning and memory as well as fear and anxiety physiology, respectively. Interestingly females do not shown significant difference in ethanol consumption and impairments in both GABA and GLU neurotransmission, we thus studied the possible protective role showed by estrogen. Animals treated with β-ethinyl estradiol and exposed to RMS showed a similar ethanol preference when compared with controls and some of RMS-induced effect on GABA and GLU neurotransmission impairment are recovered. All together, our behavioral and electrophysiological results suggest that specific stress insult during early stage of life may markedly contribute to the onset of behavioral as well as neuropsychiatric disorders occurring in adulthood.