title: The selective noradrenergic reuptake inhibitor reboxetine restores spatial learning deficits, biochemical changes, and hippocampal synaptic plasticity in an animal model of depression.
abstract: Depression is a major psychiatric illness that is associated with cognitive dysfunctions. The underlying mechanism of depression-associated memory impairment is unclear. Previously, we showed altered hippocampal synaptic plasticity in an animal model of depression. Although several antidepressants are beneficial in the treatment of depression, very little is known about the effects of these drugs on depression-associated learning and memory deficits. Prolonged antidepressant treatment might contribute to neuroplastic changes required for clinical outcomes. Accordingly, we evaluated the effect of chronic reboxetine (a selective noradrenergic reuptake inhibitor) treatment on depression-induced reduced hippocampal synaptic plasticity, neurotransmitter levels, and spatial learning and memory impairments. Depression was induced in male Wistar rats by the administration of clomipramine from postnatal days 8 to 21, and these rats were treated with reboxetine in adulthood. The neonatal clomipramine administration resulted in impaired hippocampal long-term potentiation (LTP), decreased hippocampal cholinergic activity and monoamine levels, and poor performance in a partially baited eight-arm radial maze task. Chronic reboxetine treatment restored the hippocampal LTP, acetylcholinesterase activity, and levels of biogenic amines and ameliorated spatial learning and memory deficits in the depressed state. Thus, restoration of hippocampal synaptic plasticity might be a cellular mechanism underlying the beneficial effect of reboxetine in depression-associated cognitive deficits. This study furthers the existing understanding of the effects of antidepressants on learning, memory, and synaptic plasticity and could ultimately assist in the development of better therapeutic strategies to treat depression and associated cognitive impairments.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
authors.forename: V
authors.initials: V
authors.lastname: Bhagya
authors.forename: B N
authors.initials: BN
authors.lastname: Srikumar
authors.forename: T R
authors.initials: TR
authors.lastname: Raju
authors.forename: B S
authors.initials: BS
authors.lastname: Shankaranarayana Rao
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015306:Biogenic Monoamines / Q000378:metabolism; D003863:Depression / Q000150:complications* / Q000473:pathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000188:drug therapy*; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000077593:Reboxetine; D065853:Spatial Learning / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D009025:Morpholines; D000077593:Reboxetine; D000110:Acetylcholinesterase
keywords: cognitive deficits; depression; long-term potentiation; noradrenergic dysfunction; synaptic plasticity