An integrative analysis of ethanol tolerance and withdrawal in zebrafish (Danio rerio)

The zebrafish is emerging as a popular animal model for alcohol (ethanol or EtOH) addiction due to its simplicity and practical advantages. Two phenomena associated with ethanol addiction are the development of tolerance and withdrawal. Using a multi-level approach in the current study, we characterise ethanol tolerance and withdrawal in zebrafish. We first investigate the temporal trajectory of ethanol concentration in the zebrafish brain in response to an acute exposure and during withdrawal. We report that ethanol concentrations approach a steady state within 60 min of exposure to 0.50% and 1.00% v/v ethanol and rapidly decline and return to zero within 60 min following withdrawal from chronic ethanol exposure (0.50% v/v). We characterise the changes associated with ethanol tolerance and withdrawal in zebrafish by focusing on three domains relevant to ethanol addiction: motor patterns, physiological responses (i.e. cortisol levels), and neurochemical alterations. The use of multiple domains of investigation allowed an in-depth analysis of ethanol induced changes in zebrafish.