Traumatic stress affects alcohol-drinking behavior through cocaine- and amphetamine-regulated transcript 55-102 in the paraventricular nucleus in rats

摘要

Cumulative evidence has suggested an association between stress and alcohol self-administration; however, less is known about the role of traumatic stress in alcohol drinking behavior. It has been reported that cocaine- and amphetamine-regulated transcript (CART) 55-102 may be involved in mediating stress responses and regulating reward and reinforcement. The aim of the present study was to evaluate the role of CART 55-102 in alcohol drinking behavior of rats in the presence or absence of traumatic stress. Alcohol drinking behavior was examined using the two-bottle choice drinking paradigm (one bottle contained 10% alcohol and the other contained filtered water), which was initiated 1, 3 and 7 days post-trauma (T1, T3 and T7), for 14 days in rats; the control group was initiated from T0. The results indicated that exposure to trauma significantly increased alcohol consumption and preference, particularly drinking from T3. Immunohistochemistry revealed that the lowest level of CART 55-102 immunoreactivity within the paraventricular nucleus (PVN) was exhibited in the T3 group. Additionally, an intra-PVN injection of CART 55-102 attenuated alcohol-drinking behavior in a dose-dependent manner, in the T3 group. Furthermore, the significant increase in circulating adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) concentrations in the T3 group were inhibited by CART 55-102 administration to the PVN, in particular CORT levels were significantly decreased. Positive correlations between alcohol preference and ACTH and CORT levels were also observed. These results indicated that CART 55-102 in the PVN serves an inhibitory role in traumatic stress-induced alcohol drinking behavior, possibly through disturbing hypothalamus-pituitary-adrenal axis hyperactivity.