Investigations into the behavioural and neurobiological effects of repeated ethanol withdrawal

This thesis presents a rat model, by which the effects of repeated ethanol withdrawal on withdrawal severity was investigated, in relation to the cognitive and behavioural deficits associated with repeated episodes of withdrawal. Repeated ethanol withdrawal in the rat has been well established to model the effects of repeated episodes of human alcohol detoxification. This model has enabled the study of withdrawal severity and the role of the prefrontal cortex in the form of rat behaviour. Chronic ethanol consumption led to disrupted circadian rhythm especially in measures of wakefulness and NREM sleep. However, there were no cumulative effects of multiple ethanol withdrawals. These results were confounded by altered circadian rhythms observed in the control group. Repeated ethanol withdrawal induced significantly higher levels of C-Fos, a marker of neuronal activation, compared to a single withdrawal episode. In!addition, repeated ethanol withdrawal also induced significantly higher Zif 268 expression, a marker for neuronal plasticity, in the prelimbic cortex. These findings indicated a sensitivity of prefrontal cortical areas in response to repeated ethanol withdrawal. In assessing performance on a 2-choice serial reaction time task, repeated ethanol withdrawal resulted in more sessions to criterion, indicating possible learning deficits but only when the withdrawal experience occurred prior to behavioural training and testing. Repeated ethanol withdrawal did not significantly impair attentional set shifting ability on the intradimensional/extradimensional task. The findings of this current thesis suggest that repeated ethanol withdrawal did not produce significantly severe cognitive deficits as measured by behavioural tasks sensitive to prefrontal cortical damage, despite neurobiological activation of prefrontal areas.EThOS - Electronic Theses Online ServiceGBUnited Kingdo