The 5-HT2C receptor agonist, lorcaserin, and the 5-HT6 receptor antagonist, SB-742457, promote satiety; A microstructural analysis of feeding behaviour

Abstract

Rationale: Whilst the FDA-approved anorectic, lorcaserin and various 5-hydroxytryptamine (5-HT)6 receptor antagonists reduce feeding, a direct assessment of their impact upon feeding behaviour is less clear. We therefore examined the action of lorcaserin and the clinical-stage developmental candidate 5-HT6 receptor antagonist, SB-742457, upon microstructural analysis of licking behaviour. Such analysis provides a rich source of information about the mechanisms controlling food intake. Objectives: The objective of the present study was to gain insight into the influence upon feeding behaviour of the 5-HT2C receptor agonist, lorcaserin and the developmental 5-HT6 receptor antagonist, SB-742457. Methods: The impact of lorcaserin and SB-742457 upon licking behaviour of non-deprived rats for a glucose solution was assessed using microstructural analysis. Results: Lorcaserin (0.1-3.0 mg/kg) displayed a dose-dependent ability to reduce glucose consumption via reduction in the number of bouts of licking. A similar action was evident with SB-742457, but only at the lowest dose tested (3.0 mg/kg). Conclusions: The behavioural actions of both lorcaserin and SB-742457 demonstrate they directly promote satiety.