Intermittent Ethanol Drinking Increases Intake and Reduces Anxiety-Like Behavior During Withdrawal (2014)

Undergraduates: Ayiesha Barnes, Rachel Swiver

Faculty Advisor: Sara Faccidomo
Department: Biology

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Calcium/calmodium dependent protein kinase II (CaMKII) is a post-synaptic density protein that plays a key role in neural plasticity throughout the brain. A primary goal of our research is to understand neuroadaptations in this molecular signaling protein and its association with chronic voluntary ethanol (EtOH) drinking. Our objectives were (1) to address whether a schedule of voluntary access that promotes high EtOH intake (>20g/kg/day) can elicit anxiety-like behavior during withdrawal; and (2) to elucidate the neuroadaptations in CaMKII activity occurring in reward-related brain regions associated with differing schedules of EtOH drinking. Subjects were male C57BL/6J mice, separated into three cohorts; water, continuous and intermittent EtOH groups. A voluntary 2-bottle choice paradigm was used, with water and a second bottle containing either water or EtOH was available, depending on treatment condition. After 26 days, mice in Exp. 1 were tested 8 hours into withdrawal using two behavioral measures of anxiety-like behavior. Parallel mice in Exp. 2 were rapidly decapitated 8 hours into withdrawal. Their brains were harvested and tissue from the prefrontal cortex (PFC) and amygdala (AMY) was homogenized and used for Western Blotting for tCaMKII and pCAMKII protein. Intermittent access to EtOH showed higher EtOH preference and dose consumed/day than mice with continuous access. Activity in the open field did not differ, but the mice in the continuous group had significantly more anxiety-like behavior than water drinkers in the EPM. Both schedules of EtOH intake increased phosphorylation of CaMKII alpha and beta isoforms in the PFC, and a reduction in function of tCaMKIIalpha in the AMY of intermittent drinkers only.