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Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: Implications for understanding the anti-obesity property of 5-HT2C receptor agonists

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Abstract

Rationale

The 5-HT2C receptor agonist lorcaserin (Belviq®) has been approved by the FDA for the treatment of obesity. Impulsivity is a contributory feature of some eating disorders.

Objective

Experiments investigated the effect of lorcaserin and the highly selective 5-HT2C agonist CP-809101 on measures of impulsivity and on reinstatement of food-seeking behaviour, a model of dietary relapse. The effect of both drugs on 22-h deprivation-induced feeding was also examined, as was the effect of prefeeding in each impulsivity test.

Results

Lorcaserin (0.3–0.6 mg/kg SC) and CP-809101 (0.6–1 mg/kg SC) reduced premature responding in rats trained on the 5-CSRTT and improved accuracy in a Go-NoGo task by reducing false alarms. At equivalent doses, both drugs also reduced reinstatement for food-seeking behaviour. Neither drug altered impulsive choice measured in a delay-discounting task. Lorcaserin (1–3 mg/kg SC) and CP-809101 (3–6 mg/kg SC) reduced deprivation-induced feeding but only at higher doses.

Conclusions

These results suggest that in addition to previously reported effects on satiety and reward, altered impulse control may represent a contributory factor to the anti-obesity property of 5-HT2C receptor agonists. Lorcaserin may promote weight loss by improving adherence to dietary regimens in individuals otherwise prone to relapse and may be beneficial in cases where obesity is associated with eating disorders tied to impulsive traits, such as binge eating disorder.

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Acknowledgements

We would like to thank Dr. Sandy Thevarkunnel for statistical support. With the exception of the food reinstatement experiments, all studies were funded by InterVivo Solutions Inc.

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Authors and Affiliations

  1. InterVivo Solutions Inc., 120 Carlton Street, Toronto, ON, M5A 4K2, Canada

    Guy A. Higgins & Leo B. Silenieks

  2. Vivocore, 120 Carlton Street, Toronto, ON, M5A 4K2, Canada

    Cam MacMillan

  3. Department of Psychology, Wake Forest University, Winston-Salem, NC, 27109, USA

    Everett B. Altherr & Wayne E. Pratt

  4. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 4K2, Canada

    Guy A. Higgins

  5. Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada

    Paul J. Fletcher

  6. Department of Psychology, University of Toronto, Toronto, ON, M5S 3G3, Canada

    Paul J. Fletcher

  7. Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada

    Paul J. Fletcher

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  1. Guy A. Higgins
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Correspondence to Guy A. Higgins.

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Higgins, G.A., Silenieks, L.B., Altherr, E.B. et al. Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: Implications for understanding the anti-obesity property of 5-HT2C receptor agonists. Psychopharmacology 233, 2841–2856 (2016). https://doi.org/10.1007/s00213-016-4329-3

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