PITFALLS, PROTOCOLS, AND PROSPECTS OF USING DAT KO RATS TO INVESTIGATE ALCOHOL USE DISORDER

Alcohol Use Disorder (AUD) is largely investigated with animal models such as the DAT Knockout (KO) rat. In a study investigating motivational behavior in AUD with DAT-KO rats and their wildtype we observed that the DAT-KO model consumed less sucrose and had significantly lower body weight paired with stereotaxic behaviors. Here, we aim to investigate the issues we have encountered and potential solutions for using DAT KO rats in future operant chamber paradigms. The methods of investigation were broken into three parts: Literature review, observation of animal wellbeing/behaviour, and preliminary data analyses of body weight and sucrose consumption as an indicator of wellbeing and feasibility. The literature review confirmed that issues in learning motivational tasks were observed in previous studies. Over a period of two months we identified potential wellbeing issues such as bar-mouthing, compulsive nose pokes, and anhedonia towards learning the motivational task. Finally the preliminary data analysis showed significantly reduced body weight and sucrose consumption in the DAT-KO rats compared to their wild-type.In conclusion, the validity of using DAT KO rat models to investigate AUD through operant chamber paradigms is in question. Proposed solutions include the addition of extra bedding material, chew sticks, more complex tunnel structures and stress reduction methods as a means of increasing wellbeing. Future studies should apply the proposed solutions to investigate these potential solutions deeper.