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Effect of fenfluramine on reinstatement of food seeking in female and male rats: implications for the predictive validity of the reinstatement model

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Abstract

Rationale and objectives

Relapse to old unhealthy eating habits while dieting is often provoked by stress or acute exposure to palatable foods. We adapted a rat reinstatement model, which is used to study drug relapse, to study mechanisms of relapse to palatable food seeking induced by food-pellet priming (non-contingent exposure to a small amount of food pellets) or injections of yohimbine (an alpha-2 adrenoceptor antagonist that causes stress-like responses in humans and non-humans). Here, we assessed the predictive validity of the food reinstatement model by studying the effects of fenfluramine, a serotonin releaser with known anorectic effects, on reinstatement of food seeking.

Methods

We trained food-restricted female and male rats to lever-press for 45-mg food pellets (3-h sessions) and first assessed the effect of fenfluramine (0.75, 1.5, and 3.0 mg/kg, i.p.) on food-reinforced responding. Subsequently, we extinguished the food-reinforced responding and tested the effect of fenfluramine (1.5 and 3.0 mg/kg) on reinstatement of food seeking induced by yohimbine injections (2 mg/kg, i.p.) or pellet priming (four non-contingent pellets).

Results

Fenfluramine decreased yohimbine- and pellet-priming-induced reinstatement. As expected, fenfluramine also decreased food-reinforced responding, but a control condition in which we assessed fenfluramine's effect on high-rate operant responding indicated that the drug's effect on reinstatement was not due to performance deficits.

Conclusions

The present data support the predictive validity of the food reinstatement model and suggest that this model could be used to identify medications for prevention of relapse induced by stress or acute exposure to palatable food during dietary treatments.

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Acknowledgments

The work was supported by the Intramural Research Program of the National Institute on Drug Abuse. CLP, CC, and BMN equally contributed to this paper.

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  1. Intramural Research Program, NIDA/NIH, Baltimore, MD, USA

    Charles L. Pickens, Carlo Cifani, Brittany M. Navarre, Hila Eichenbaum, Florence R. Theberge, Michael H. Baumann, Donna J. Calu & Yavin Shaham

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  1. Charles L. Pickens
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  2. Carlo Cifani
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  3. Brittany M. Navarre
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  8. Yavin Shaham
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Correspondence to Charles L. Pickens or Yavin Shaham.

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Pickens, C.L., Cifani, C., Navarre, B.M. et al. Effect of fenfluramine on reinstatement of food seeking in female and male rats: implications for the predictive validity of the reinstatement model. Psychopharmacology 221, 341–353 (2012). https://doi.org/10.1007/s00213-011-2585-9

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