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Simultaneous anhedonia and exaggerated locomotor activation in an animal model of depression

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Abstract

Rationale

Anhedonia, or hyposensitivity to normally pleasurable stimuli, is a cardinal symptom of depression. As such, reward circuitry may comprise a substrate with relevance to this symptom of depression.

Objectives

Our aim was to characterize in the rat changes in the rewarding properties of a pharmacological and a natural stimulus following olfactory bulbectomy (OBX), a pre-clinical animal model of depression.

Methods

We measured amphetamine enhancement of brain stimulation reward, changes in sucrose intake, as well as striatal cAMP response element binding protein (CREB) activity, a molecular index previously associated with depressant-like behavior. Moreover, since alteration of psychomotor activity is also a common symptom of depression, and psychostimulant reward and locomotion are thought to share common neurobiology, we used the same treatment schedule of amphetamine to probe for changes in locomotion.

Results

Our findings show that OBX produces a behavioral phenotype characterized by both anhedonia and exaggerated locomotor activation. Thus, we observed a blunted response to the rewarding properties of amphetamine (1 mg/kg, 21 days post-lesion), a long-lasting reduction in sucrose intake and increased striatal CREB activity. In addition, the same dose of amphetamine, at a coincident time post-lesion, triggered an exaggerated response to its locomotor-stimulant actions.

Conclusions

These paradoxical findings are not consistent with the notion that reward and locomotion are mediated by a common substrate; this dissociation may be useful in modeling psychiatric disorders such as mixed depressive states. In addition, our findings suggest that central reward circuitry may constitute a possible target for rationally designed therapeutics for depression.

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Acknowledgments

This study was supported by the Canadian Psychiatric Research Foundation (SMB), Canadian Institutes of Health Research (GP), and the Natural Sciences and Engineering Research Council of Canada (SMB, GP). SMB and GP hold salary awards and OM-F a postdoctoral fellowship from the Fonds de Recherche en Santé du Québec. The authors are grateful to AstraZeneca (USA) for financial contribution to this work and to Grant S Vallinis for help with video recording analyses.

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Authors and Affiliations

  1. Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada

    Thomas Romeas, Ouissame Mnie-Filali & Graciela Piñeyro

  2. Department of Psychiatry, University of Montreal, Montreal, Quebec, Canada

    Marie-Claude Morissette, Graciela Piñeyro & Sandra M. Boye

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  1. Thomas Romeas
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  2. Marie-Claude Morissette
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  3. Ouissame Mnie-Filali
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  4. Graciela Piñeyro
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  5. Sandra M. Boye
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Correspondence to Sandra M. Boye.

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Romeas, T., Morissette, MC., Mnie-Filali, O. et al. Simultaneous anhedonia and exaggerated locomotor activation in an animal model of depression. Psychopharmacology 205, 293–303 (2009). https://doi.org/10.1007/s00213-009-1539-y

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  • DOI: https://doi.org/10.1007/s00213-009-1539-y

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