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Oxotremorine treatment restores hippocampal neurogenesis and ameliorates depression-like behaviour in chronically stressed rats

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Abstract

Rationale

Chronic stress results in cognitive impairment, affects hippocampal neurogenesis and is known to precipitate affective disorders such as depression. In addition to stress, neurotransmitters such as acetylcholine (ACh) modulate adult neurogenesis. Earlier, we have shown that oxotremorine, a cholinergic muscarinic agonist, ameliorates stress-induced cognitive impairment and restores cholinergic function.

Objectives

In the current study, we have looked into the possible involvement of adult neurogenesis in cognitive restoration by oxotremorine. Further, we have assessed the effect of oxotremorine treatment on depression-like behaviour and hippocampal volumes in stressed animals.

Methods

Chronic restraint stressed rats were treated with either vehicle or oxotremorine. For neurogenesis studies, proliferation, survival and differentiation of the progenitor cells in the hippocampus were examined using 5′-bromo-2-deoxyuridine immunohistochemistry. Depression-like behaviour was evaluated using forced swim test (FST) and sucrose consumption test (SCT). Volumes were estimated using Cavalieri’s estimator.

Results

Hippocampal neurogenesis was severely decreased in stressed rats. Ten days of oxotremorine treatment to stressed animals partially restored proliferation and survival, while it completely restored the differentiation of the newly formed cells. Stressed rats showed increased immobility and decreased sucrose preference in the FST and SCT, respectively, and oxotremorine ameliorated this depression-like behaviour. In addition, oxotremorine treatment recovered the stress-induced decrease in hippocampal volume.

Conclusions

These results indicate that the restoration of impaired neurogenesis and hippocampal volume could be associated with the behavioural recovery by oxotremorine. Our results imply the muscarinic regulation of adult neurogenesis and incite the potential utility of cholinomimetics in ameliorating cognitive dysfunction in stress-related disorders.

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Acknowledgements

This work is supported by the Department of Science and Technology, Department of Biotechnology, Government of India, New Delhi, India (to BSSR). JV was supported by a Research Fellowship from the Council of Scientific and Industrial Research (CSIR), Government of India, and KM was supported by a Research Fellowship from the University Grants commission (UGC), Government of India.

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Author notes

  1. J. Veena

    Present address: Laboratoire NutriNeuro, UMR INRA 1286, CNRS 5226, Université Bordeaux 2, Bâtiment UFR Pharmacie, 33076, Bordeaux Cedex, France

  2. B. N. Srikumar

    Present address: Interdisciplinary Institute for Neuroscience, Univ. de Bordeaux, UMR 5297, 33077, Bordeaux Cedex, France

Authors and Affiliations

  1. Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Road, PB # 2900, Bangalore, 560 029, India

    J. Veena, B. N. Srikumar, K. Mahati, T. R. Raju & B. S. Shankaranarayana Rao

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  1. J. Veena
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  2. B. N. Srikumar
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  3. K. Mahati
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  4. T. R. Raju
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  5. B. S. Shankaranarayana Rao
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Correspondence to B. S. Shankaranarayana Rao.

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Veena, J., Srikumar, B.N., Mahati, K. et al. Oxotremorine treatment restores hippocampal neurogenesis and ameliorates depression-like behaviour in chronically stressed rats. Psychopharmacology 217, 239–253 (2011). https://doi.org/10.1007/s00213-011-2279-3

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  • DOI: https://doi.org/10.1007/s00213-011-2279-3

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