A high fructose diet does not affect amphetamine self-administration or spatial water maze learning and memory in female rats.

High energy diets can have a detrimental effect on brain plasticity. For example, a high fructose diet impairs spatial memory in male rats. The aim of the present study was to determine whether a high fructose diet impairs another form of learning and memory: drug reinforcement learning. Female Sprague-Dawley rats were fed a high fructose diet (60%) from weaning at postnatal day (PND) 21, then allowed to acquire lever-pressing maintained by intravenous (i.v.) amphetamine at PND 68, 109, or 165. Acquisition was tested on a fixed ratio one (FR1) schedule of reinforcement (0.025 mg/kg/infusion, 1h daily sessions, 10 sessions over 14 days), followed by testing for reinforcing efficacy on a progressive ratio (PR) schedule (0.025, 0.01, and 0.1mg/kg/infusion), 14 days of abstinence, and within-session extinction and reinstatement tests. Subsequently, water maze acquisition and retention were tested in these subjects as well as a separate cohort tested in the water maze only. The diet had no effect on acquisition, reinforcing efficacy, extinction, or reinstatement of amphetamine seeking. Nor did the diet alter any measures of spatial memory. The high fructose diet did decrease body mass and increase relative liver and spleen mass, but did not affect plasma triglyceride concentrations consistently. Together with prior research on males, these results suggest that the metabolism of fructose and the effects of a high fructose diet on learning and memory may be sex-dependent.