5‐HT2C antagonism blocks blood oxygen level‐dependent pharmacological‐challenge magnetic resonance imaging signal in rat brain areas related to feeding

AbstractIn this study, pharmacological‐challenge magnetic resonance imaging was used to further characterize the central action of serotonin on feeding. In both feeding and pharmacological‐challenge magnetic resonance imaging experiments, we combined 5‐HT1B/2C agonist m‐chlorophenylpiperazine (mCPP) challenge with pre‐treatment with the selective 5‐HT1B and 5‐HT2C receptor antagonists, SB 224289 (2.5 mg/kg) and SB 242084 (2 mg/kg), respectively. Subcutaneous injection of mCPP (3 mg/kg) completely blocked fast‐induced refeeding in freely behaving, non‐anaesthetized male rats, an effect that was not modified by the 5‐HT1B receptor antagonist but was partially reversed by the 5‐HT2C receptor antagonist. mCPP alone induced both positive and negative blood oxygen level‐dependent (BOLD) responses in the brains of anaesthetized rats, including in the limbic system and basal ganglia. Overall, the 5‐HT2C antagonist SB 242084 reversed the effects elicited by mCPP, whereas the 5‐HT1B antagonist SB 224289 had virtually no impact. SB 242084 eliminated BOLD signal in nuclei associated with the limbic system and diminished activation in basal ganglia. In addition, BOLD signal was returned to baseline levels in the cortical regions and cerebellum. These results suggest that mCPP may reduce food intake by acting specifically on brain circuits that are modulated by 5‐HT2C receptors in the rat.