Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula

We previously reported that a human insulin transgene was specifically expressed in the medial habenula of the adult mouse brain, and that this expression was ascribed to the delta-168 transgene. The present study analyses the possible behavioural consequences of this insulin transgene expression using measures of food intake, spontaneous activity, emotional reactivity, learning and extinction performance of an operant task. The delta-168 transgenic mice did not differ from the C57BL/6 control mice as concerns food intake, behaviour in the open field, or emotional response in an elevated plus maze. On the other hand, measures of locomotor activity in a circular corridor revealed a significantly faster decline of spontaneous locomotor activity in male as compared to female delta-168 transgenic mice. Moreover, as compared to female transgenic mice, male transgenic mice exhibited a deficit in the rate of acquisition and an acceleration of the rate of extinction of a bar press response in a Skinner box. In contrast, the behaviour of female transgenic mice did not differ from either male or female C57BL/6 control mice. The results of the present study demonstrate that the behavioural modifications observed in delta-168 transgenic mice are sex-linked and suggest that these behavioural differences result from changes in the interaction (interface) between motivational and motor mechanisms mediated via the striato-habenulo-mesencephalic system.