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Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats

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Abstract

Rationale

Substance P receptor [neurokinin1 (NK1-R)] antagonists and melatonin1/2 receptor (MT1/2-R) agonists have been claimed to be potential antidepressants (ADs). In animals, these compounds are active in validated models responsive to ADs, such as forced swimming test and chronic mild stress paradigms. Classical AD drugs are also known to be effective in pathologies characterized by an impulse control deficiency. In line with this clinical observation, previous studies demonstrated that classical ADs increased the capacity to wait for food reward in rats subjected to a paradigm aimed at assessing impulsive-related behaviour.

Objectives

This study was conducted to investigate the effects of two MT1/2-R agonists, melatonin and agomelatine, and a NK1-R antagonist, GR205171, on tolerance to delay of food reward in rats.

Methods

Fasting rats were trained in a T-maze and allowed to choose between two magnitudes of reward: immediate but small reward (two pellets) vs 25-s delayed but large reward (ten pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reinforcer in less than 40% of the trials.

Results

Like the established ADs clomipramine (8 mg kg−1, i.p.) and fluvoxamine (4 mg kg−1, i.p.), melatonin (3 and 10 mg kg−1, i.p.), agomelatine (10 and 30 mg kg−1, i.p.) and GR205171 (30 mg kg−1 but not 10 mg kg−1, s.c.) significantly increased the number of choices of the large-but-delayed reward. The effect of melatonin (3 mg kg−1, i.p.) was not counteracted by the MT1/2-R antagonist S22153 (40 mg kg−1, i.p.) that exerted no effect on its own.

Conclusion

These results suggest that MT1/2-R agonists and NK1-R antagonists enhance rats' tolerance to delay of gratification, an effect which may reflect their ability to improve impulse control. Further investigations are necessary to clarify the neurobiological mechanisms responsible for this effect.

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Acknowledgements

This research was supported by grants from INSERM and LSHM-CT-2003-503474 CEE contract “Newmood”. We are grateful to pharmaceutical companies (GlaxoSmithKline, Hoffmann La-Roche, Novartis, Servier, Solvay-Duphar) for generous gifts of drugs. Florence Loiseau was a recipient of fellowships of the French Ministry of Education and Research, and the Fondation Recherche Médicale during the course of this work.

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  1. INSERM U.677 (ex U.288), Faculty of Medicine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634, Paris, Cedex 13, France

    Florence Loiseau, Michel Hamon & Marie-Hélène Thiébot

  2. Department of Pharmacology, Faculty of Medicine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634, Paris, Cedex 13, France

    Claudine Le Bihan

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  1. Florence Loiseau
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  2. Claudine Le Bihan
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Correspondence to Marie-Hélène Thiébot.

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Loiseau, F., Le Bihan, C., Hamon, M. et al. Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats. Psychopharmacology 182, 24–32 (2005). https://doi.org/10.1007/s00213-005-0050-3

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