Dose- and time-dependent effects of the dual GIP/GLP-1 receptor agonist tirzepatide on emotional overeating in a rat model of intracranial self-stimulation

Abstract

Background. Despite the increasing prevalence of emotional overeating and obesity, the specific neurohormonal mechanisms involved in the pathogenesis of these pathological processes remain poorly understood. The incretin system may serve as an important therapeutic target for the correction of these eating disorders. Aim . To study the effects of the dual GIP/GLP-1 receptor agonist tirzepatide on feeding behavior parameters in a rat model of emotional overeating induced by intracranial self-stimulation (ICSS). Methods . Experiments were performed on male Wistar rats with electrodes implanted in the ventral tegmental area. Tirzepatide was administered subcutaneously at doses of 0.05, 0.10, and 0.30 mg/kg for 7 days. Food intake (number of seeds consumed) was assessed at 1 minute, 30 minutes, and on days 3 and 7 after administration. Results . No statistically significant changes in feeding activity were observed 30 minutes after tirzepatide administration. On the third day, a decrease in food intake was observed only at the maximum dose (0.30 mg/kg). On the seventh day, a significant anorexigenic effect was observed at doses of 0.10 and 0.30 mg/kg, indicating a doseand time-dependent effect. Conclusion . Tirzepatide does not exert a significant acute effect on feeding activity in the emotional overeating model at 30 minutes after administration. Repeated administration of the drug revealed a doseand time-dependent anorexigenic effect, manifested by a decrease in food intake on days 3 and 7 of the experiment. The most pronounced decrease in feeding activity was observed at doses of 0.10 and 0.30 mg/kg on day 7.