Involvement of 5‐HT 2C Receptors in the Regulation of Food Intake in Siberian Hamsters

The Siberian hamster provides a physiological model for understanding the hypothalamic control of energy metabolism as it undergoes annual photoperiod‐regulated cycles of body weight (i.e. fattening in summer, and catabolism of fat stores in winter). As a first step to investigate whether enhanced serotonergic (5‐HT) tone might underlie the catabolic processes in short days, we investigated whether serotonergic stimulation can produce catabolic actions in fat hamsters housed in long days. Acute treatment with the serotonin reuptake inhibitor (+/–) fenfluramine (8 mg/kg, i.p.) produced a prolonged, dose‐dependent reduction in food intake in both photoperiods. Behavioural observations and radiotelemetry analyses revealed that this anorectic effect of fenfluramine was associated with short‐term increases in locomotor activity and in core body temperature. In a subsequent series of studies, hamsters were pretreated with the 5‐HT 2C receptor antagonist SB242084 (4 mg/kg, i.p.). This 5‐HT 2C receptor antagonist completely blocked the anorectic actions of fenfluramine, but did not decrease the hyperthermia or hyperlocomotion induced by fenfluramine; thus, the anorectic actions of fenfluramine probably reflect actions via the 5‐HT 2C receptor. Consistent with these observations, treatment of hamsters with the 5‐HT 2C receptor agonist VER 3323 (10 mg/kg, i.p.) or the 5‐HT 1B/2C receptor agonist mCPP (3 mg/kg, i.p.) reduced food intake. The response to manipulation of serotonergic pathways was not affected by the ambient photoperiod in any of these studies. We conclude that the anorectic actions of fenfluramine are not an indirect consequence of serotonergic actions on arousal pathways, and that its actions on feeding in the Siberian hamster are most likely to be mediated by the 5‐HT 2C receptor.