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Evaluation of reward processes in an animal model of depression

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Abstract

Rationale

Anhedonia is a core symptom of major depression. Deficits in reward function, which underlie anhedonia, can be readily assessed in animals. Therefore, anhedonia may serve as an endophenotype for understanding the neural circuitry and molecular pathways underlying depression.

Objective

Surprisingly, there is scant knowledge regarding alterations in brain reward function after olfactory bulbectomy (OB), an animal model which results in a behavioural syndrome responsive to chronic antidepressant treatment. Therefore, the present studies aimed to assess reward function after bulbectomy.

Materials and methods

The present study utilized sucrose preference, cocaine-induced hyperlocomotion and intra-cranial self-stimulation (ICSS) responding to examine reward processes in the OB model.

Results

Bulbectomized animals showed a marked preference (>90%) for 0.8% sucrose solution compared with water; similar to the preference exhibited by sham controls. Importantly, there were pronounced deficits in brain reward function, as assessed using ICSS, which lasted 8 days before returning to baseline levels. Furthermore, bulbectomized animals were hyper-responsive to the locomotor stimulating properties of an acute and a repeated cocaine regimen. However, no difference in ICSS facilitation was observed in response to an acute cocaine injection.

Conclusions

Taken together, these results suggest that bulbectomized rats display alterations in brain reward function, but these changes are not long-lasting and thus, not amenable to investigating the effects of pharmacological interventions. However, given that OB animals are hypersensitive to drugs of abuse, bulbectomy may be an appropriate inducing factor for the development of animal models of co-morbid depression and drug dependence.

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Acknowledgement

The authors would like to thank Dr Cedric Mombereau, Hugo Buerki and Stefan Imobersteg for their technical assistance and Mr. Mike Arends for editorial assistance. This work was supported by National Institutes of Mental Health/National Institute on Drug Abuse Grant U01 MH69062.

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Author notes

  1. David A. Slattery

    Present address: Institute of Zoology, University of Regensburg, Regensburg, Germany

Authors and Affiliations

  1. Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

    David A. Slattery & John F. Cryan

  2. Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA

    Athina Markou

  3. Department of Pharmacology and Therapeutics, School of Pharmacy, University College Cork, Cork, Ireland

    John F. Cryan

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  1. David A. Slattery
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  2. Athina Markou
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Correspondence to John F. Cryan.

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Slattery, D.A., Markou, A. & Cryan, J.F. Evaluation of reward processes in an animal model of depression. Psychopharmacology 190, 555–568 (2007). https://doi.org/10.1007/s00213-006-0630-x

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  • DOI: https://doi.org/10.1007/s00213-006-0630-x

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