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A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine

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Abstract

Rationale

Procedures for studying the effects of medications on satiation will assist the development of obesity medications.

Objectives

Develop a procedure for measuring satiation during consumption of bland and highly palatable food and determine the effect of acute intramuscular administration of dexfenfluramine (DFEN), which increases serotonin levels, and memantine (MEM), which blocks N-methyl-d-aspartate receptors.

Materials and methods

A modified progressive ratio (PR) procedure was used to track changes in reinforcing strength when a food was consumed. The response requirement increased after each reinforcement, and reinforcing strength was estimated using the breakpoint (BP), which was the last completed response cost. There was one preferred food (sweet candy) and one chow pellet PR session per week. During each session, four male and four female adult baboons experienced three 1-h PR trials, separated by 30 min. Chow pellets were available at all other times. We examined the BP for one to 20 candies or chow pellets. Drug effects were examined when baboons had access to one and ten candies or chow pellets.

Results

BPs for candy were greater than for pellets. Varying the pellet/candy pieces per delivery produced an inverted U-shaped function on the first trial, i.e., maximal BP was observed for three items, and the BP for multiple items, but not a single item, decreased across trials, i.e., BP decreased with food intake and satiation. DFEN and MEM decreased responding with the greatest effects at ten deliveries, suggesting that DFEN and MEM enhanced satiation.

Conclusion

Drugs that enhance satiation for several types of food may be particularly effective for decreasing food intake.

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Acknowledgements

This research was supported by DA-04130 from The National Institute on Drug Abuse and MH-65024 from the National Institute on Mental Health, and approved by the New York State Psychiatric Institute Animal Care and Use Committee. Merz Pharmaceuticals provided the memantine and an unrestricted gift to Columbia University in support of the laboratory. The assistance of Jean Willi, April Modrzakowski, Angel Ramirez, Aaisha Mirza, Sean Ortman, and Drs. Suzette Evans and Mohamed Osman is gratefully acknowledged.

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Authors and Affiliations

  1. Division on Substance Abuse, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 12066, New York, NY, 10032, USA

    Richard W. Foltin & Adam Bisaga

  2. Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA

    Richard W. Foltin & Adam Bisaga

  3. Merz Pharmaceuticals GmbH, Eckenheimer Landstraße 100, 60318, Frankfurt am Main, Germany

    Wojciech Danysz

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  1. Richard W. Foltin
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Correspondence to Richard W. Foltin.

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Foltin, R.W., Danysz, W. & Bisaga, A. A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine. Psychopharmacology 199, 583–592 (2008). https://doi.org/10.1007/s00213-008-1178-8

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  • DOI: https://doi.org/10.1007/s00213-008-1178-8

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