Intrahypothalamic paraventricular nucleus-microinjected SKF 38393, D1 receptor agonist, reduces food intake in 24 hours food-deprived rats

Introduction: Dopamine plays an important role in the central nervous system for modulating food intake. Dopamine receptors are distributed within the hypothalamus, and expression of D1 receptors is significant in hypothalamic paraventricular nucleus (PVN). Therefore, the aim of this study was to find if PVN-microinjected SKF38393, D1 receptor agonist, may modulate food intake. Methods: Guide cannula directed to the PVN were implanted in male Wistar rats (220-250 g). Stereotaxic coordinates were: lateral: +0.4 mm from midline dorsoventral: 7 mm from skull surface anteroposterior: -1.8 mm from the bregma. Intra-PVN microinjections of SKF38393, SCH23390 (D1 receptor antagonist) and saline were performed after a 5-7 day recovery period. Hourly over a 3 hours period, the weight of food pellets was measured. Assessment of spontaneous activity in rat was performed in standard activity chambers interfaced with a Digiscan animal. Feeding trials were done normally from Saturday to Wednesday between 9:00 am and 12:00 on rats which were deprived of food for 24 hours. All drugs were administered in 0.9% saline. Results: Intraparaventricular injections of SKF38393 (0.06, 0.01 μg) decreased food intake in a dose-dependent manner. The PVN injection of SCH23390, D1 receptor antagonist, did not affect food intake decreased by PVNmicroinjected SKF38393 (0.01 μg). Analysis of the physical activity revealed that PVN microinjection of SKF38393 (0.01 μg) did not affect locomotor activity. Conclusion: Our results showed that PVN-microinjected SKF38393 decreases food intake. This suppressive effect is probably not mediated through D1 receptors.