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Dexfenfluramine and feeding reward
B G Hoebel1, L Hernandez, R C McClelland
1Department of Psychology, Princeton University, New Jersey 08544.
Clinical Neuropharmacology
|January 1, 1988
Summary
Dexfenfluramine, a serotonin-releasing agent, inhibits the lateral hypothalamic feeding-reward system. This compound selectively reduces self-stimulation, offering a targeted approach to appetite control.
Area of Science:
- Neuroscience
- Pharmacology
- Appetite Regulation
Background:
- The lateral hypothalamic (LH) feeding-reward system is crucial for motivated feeding behaviors.
- The mesolimbic dopamine system in the ventral tegmental area (VTA) is implicated in reward and self-administration.
- Physiological signals like satiety and body weight modulate feeding-reward system activity.
Purpose of the Study:
- To investigate the effects of dexfenfluramine on the LH feeding-reward system.
- To differentiate the effects of dexfenfluramine from racemic fenfluramine on self-stimulation and stimulation-escape.
- To explore the neurochemical mechanisms underlying dexfenfluramine's action.
Main Methods:
- Review of background experiments and new findings.
- Behavioral assays measuring self-stimulation and stimulation-escape.
- Microdialysis to measure neurotransmitter release in the LH.
Main Results:
- Dexfenfluramine selectively inhibited LH self-stimulation, unlike racemic fenfluramine which caused lethargy.
- Dexfenfluramine did not affect stimulation-escape responses.
- Microdialysis confirmed that dexfenfluramine releases serotonin in the LH.
Conclusions:
- Dexfenfluramine's inhibition of the feeding-reward system is mediated by serotonin release in the LH.
- The d-isomer (dexfenfluramine) offers a more specific effect on feeding reward compared to racemic fenfluramine.
- Serotonin release by dexfenfluramine may inhibit circuitry involved in feeding reward.