It is known that cannabinoids modulate feeding behavior in humans and rodent animal models. This may be due, in part, to cannabinoid interactions with the hypothalamic feeding circuitry. Several components of this neuronal network are sexually differentiated and steroid sensitive, and sex differences in the cannabinoid-induced consumption of palatable foods have been reported. Moreover, socioepidemiologic evidence points to obvious gender differences in feeding behavior; for example, females have a greater propensity toward having eating disorders, such as anorexia nervosa and bulimia. The present study used a guinea pig animal model to systematically evaluate potential sex differences in intrinsic feeding behavior between males and females, as well as sex differences in the cannabinoid-induced increase in feeding behavior. Experiments were performed using a comprehensive laboratory animal monitoring system (CLAMS), which enables the quantification of parameters such as food intake, meal frequency, meal duration, and the amount of food eaten per meal. After a 3-day acclimation period, animals were weighed and injected with either the CB1 receptor agonist (1 mg/kg, SC) or its cremophore/ethanol/saline vehicle (1/1/18; 0.1 mL/kg, SC) each day for 7 days. Whereas female guinea pigs showed a greater basal meal duration, male animals exhibited a more robust cannabinoid-induced increase in food intake, meal duration, and the amount of food per meal. On the other hand, cannabinoids decreased meal frequency to a similar extent in both males and females. From these data, it is apparent that the cannabinoid-induced increase in feeding behavior is mediated in a sexually differentiated manner. These results are in accordance with previous electrophysiologic studies in which the receptor-mediated modulation of an A-type potassium current was determined to be sex specific.
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