Effects of nefazodone on voluntary ethanol consumption induced by isolation stress in young and aged rats.

Late-onset ethanol (EtOH) consumption is related to life and social stressors of aging. The stress system (hypothalamic-pituitary-adrenal, HPA, axis) coordinates the adaptive response of the organism to stressors, but age-related deficits in HPA function seem to be associated with disorders such as late-onset EtOH consumption, anxiety and depression. In the present study, we examined whether HPA dysfunction is associated with stress-related EtOH consumption in aged rats and whether the treatment with nefazodone hydrochloride, a phenylpiperazine antidepressant, partially reverses the adverse effects of isolation (ISOL) stress. The animals were offered two-bottle choice consumption of 0.2% saccharin and 10% EtOH/0.2% saccharin, and then exposed to 4 days of ISOL stress on an irregular, unpredictable schedule. ISOL stress-induced increases in corticosterone secretion and EtOH consumption both during and following the stress (recovery period) in aged rats. Nevertheless, this effect at the recovery period was not evident in young stressed rats. Nefazodone caused a significant decrease in plasma corticosterone levels and EtOH consumption. The attenuation of stress-induced corticosterone by nefazodone was correlated with reduced EtOH consumption. These findings link the effect of ISOL stress to the induction of voluntary EtOH consumption following the end of the stressor and the limitation of aged HPA to down-regulated corticosterone.