Gossypol's effects on ingestive behaviour in mice: The first step in a systematic process to define gossypol's suitability for use in murine pest management

Abstract

Gossypol, synthesised by the cotton plant, Gossypium, causes physiological and behavioural changes in mammals, suggesting it may be suitable for murine pest management. One of the most under-studied responses to gossypol, especially in the house mouse, Mus musculus, is its effect on ingestive behaviour, with some authors reporting anorexia and others observing no effect on energy metabolism. Importantly, there has been no systematic analysis of gossypol’s effect on food intake in mice. Therefore, the goal of this thesis was to provide the initial step in defining gossypol’s effect on feeding behaviour in mice by observing their responses after exposure to precise doses of gossypol delivered via injection. Mice underwent two injection intraperitoneal (IP) paradigms; acute and chronic (11 daily injections) exposures to 0 (vehicle), 10, 30, 100 and 300 mg/kg b.wt., and 0 (vehicle) and 100 mg/kg b.wt. respectively. The intakes of bland (chow) and palatable tastants were measured during the acute exposure. An increase in chow intake was observed at 1 and 3 hr post-exposure with 300 mg/kg b.wt. dose. An increase in glucose intake was also observed in mice injected with 100 mg/kg b.wt. at 1 and 12 hr post-exposure. Neither of these hyperphagia responses showed a complementary increase in body weight. During the chronic exposure, body weight and chow intake were measured throughout the injection period and on select days of the 40 day post-exposure period. While there was no difference in food intake and body weight during the gossypol exposure, on day 10 post-exposure, food intake had increased by 50% and was still elevated on day 40, but no differences in body weight were noted. To examine whether this increase in food intake was an effect of a long-term anxiogenic response associated with a likely post-exposure malaise, several anxiety assessment tests were performed, showing no change. This thesis shows that gossypol affects feeding behaviour in mice. Interestingly, no anorexigenic effect was observed, but in fact moderate hyperphagia without changes in body weight was shown in both acute and chronic paradigms. The data from this thesis can be built upon with future studies using oral administration to develop the understanding of this important aspect of gossypol and to more precisely determine gossypol’s suitability for enhancing murine pest management.