• V Bhagya, B N Srikumar, T R Raju, and RaoB S ShankaranarayanaBS.
• Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Road, PB # 2900, Bangalore, 560 029, India.
• Psychopharmacology (Berl.). 2011 Mar 1; 214 (2): 477-94.

RationaleThe 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.ObjectivesTo 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.ResultsFourteen 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.ConclusionsThus, 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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