Cocaine hypophagia and hyperlocomotion in rats before and after exposure to a high-fat diet

Relatively few studies have examined the effects of psychostimulants in obese subjects. Using the dietary obese rat model, the present experiments determined the reductions in food intake (hypophagia) and increases in locomotion (hyperlocomotion) induced by cocaine in diet-induced obese prone (DIO-prone) rats and diet resistant prone (DR-prone) rats as well as diet-induced obese (DIO) rats and diet resistant (DR) rats. In Experiment 1, thirty-six male Sprague-Dawley rats were given intra-peritoneal (i.p.) injections of cocaine (0, 10, 20, and 30 mg/kg) immediately prior to placement into locomotor chambers outfitted with a food source and a water source for a 60-minute test period. In Experiment 2, the same rats were exposed to a high-fat diet, and were subsequently divided into groups according to the extent of the weight gain (high weight gainers ? DIO group, low weight gainers ? DR group, and residual weight gainers ? MIX group). The rats were retested for reactivity to cocaine using conditions similar to those in Experiment 1. Rats injected with cocaine prior to high-fat exposure (Experiment 1) showed a dose dependent suppression of food intake, as well as a dose dependent increase in locomotor activity, with DR-prone rats exhibiting an enhanced degree of cocaine-induced hypophagia, as well as cocaine-induced hyperlocomotion as compared to the other groups. In Experiment 2, DIO rats exhibited a suppression of food intake after injection of 10 mg/kg cocaine, as well as an increase in locomotor activity that was significantly greater than noted in the other groups. When the results of Experiment 1 were analyzed as a function of prospective body weight gain (as opposed to placement into distinct groups), reactivity to cocaine decreased as body weight gain increased. In contrast, after high-fat exposure and weight gain, increased body weight gain was associated with an increased magnitude of suppression in food intake after cocaine administration. Similar patterns of differential cocaine sensitivity were observed for cocaine hyperlocomotion in Experiment 2. These studies indicate that although the propensity to develop obesity is associated with a diminished cocaine response, cocaine reactivity is enhanced after the induction of obesity.