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Chronic escitalopram treatment restores spatial learning, monoamine levels, and hippocampal long-term potentiation in an animal model of depression

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Abstract

Rationale

The neural basis of depression-associated cognitive impairment remains poorly understood, and the effect of antidepressants on learning and synaptic plasticity in animal models of depression is unknown. In our previous study, learning was impaired in the neonatal clomipramine model of endogenous depression. However, it is not known whether the cognitive impairment in this model responds to antidepressant treatment, and the electrophysiological and neurochemical bases remain to be determined.

Objectives

To address this, we assessed the effects of escitalopram treatment on spatial learning and memory in the partially baited radial arm maze (RAM) task and long-term potentiation (LTP) in the Schaffer collateral-CA1 synapses in neonatal clomipramine-exposed rats. Also, alterations in the levels of biogenic amines and acetylcholinesterase (AChE) activity were estimated.

Results

Fourteen days of escitalopram treatment restored the mobility and preference to sucrose water in the forced swim and sucrose consumption tests, respectively. The learning impairment in the RAM was reversed by escitalopram treatment. Interestingly, CA1-LTP was decreased in the neonatal clomipramine-exposed rats, which was restored by escitalopram treatment. Monoamine levels and AChE activity were decreased in several brain regions, which were restored by chronic escitalopram treatment.

Conclusions

Thus, we demonstrate that hippocampal LTP is decreased in this animal model of depression, possibly explaining the learning deficits. Further, the reversal of learning and electrophysiological impairments by escitalopram reveals the important therapeutic effects of escitalopram that could benefit patients suffering from depression.

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Acknowledgments

We acknowledge the financial support from the Council of Scientific and Industrial Research (CSIR), New Delhi, India through a research fellowship to BV. Escitalopram was a gift from Sun Pharmaceuticals & Glenmark Pharmaceuticals, Mumbai, India. The authors thank Dr. Veena Jayagopalan and Ms. Mahati Krishna for their technical assistance in the neurochemistry experiments.

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  1. B. N. Srikumar

    Present address: Laboratoire “Physiologie Cellulaire de la Synapse”, UMR 5091 CNRS, Université Bordeaux 2 Institut François Magendie, Bordeaux Cedex, 33077, 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

    V. Bhagya, B. N. Srikumar, T. R. Raju & B. S. Shankaranarayana Rao

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  1. V. Bhagya
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  2. B. N. Srikumar
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  3. T. R. Raju
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  4. B. S. Shankaranarayana Rao
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Correspondence to B. S. Shankaranarayana Rao.

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Bhagya, V., Srikumar, B.N., Raju, T.R. et al. Chronic escitalopram treatment restores spatial learning, monoamine levels, and hippocampal long-term potentiation in an animal model of depression. Psychopharmacology 214, 477–494 (2011). https://doi.org/10.1007/s00213-010-2054-x

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