{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:27:50Z","timestamp":1785774470066,"version":"3.56.0"},"reference-count":122,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T00:00:00Z","timestamp":1408579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Council of Scientific and Industrial Research (CSIR), New Delhi, India for Senior Research Associateship to BV"},{"name":"Department of Biotechnology (DBT), Government of India"},{"name":"Department of Science and Technology (DST), Government of India, New Delhi, India"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>Depression is a major psychiatric illness that is associated with cognitive dysfunctions. The underlying mechanism of depression\u2010associated 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\u2010associated 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\u2010induced 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\u2010term potentiation (LTP), decreased hippocampal cholinergic activity and monoamine levels, and poor performance in a partially baited eight\u2010arm 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\u2010associated 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. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23473","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T15:43:16Z","timestamp":1408635796000},"page":"104-120","source":"Crossref","is-referenced-by-count":21,"title":["The selective noradrenergic reuptake inhibitor reboxetine restores spatial learning deficits, biochemical changes, and hippocampal synaptic plasticity in an animal model of depression"],"prefix":"10.1002","volume":"93","author":[{"given":"V.","family":"Bhagya","sequence":"first","affiliation":[{"name":"Department of Neurophysiology National Institute of Mental Health and Neuro Sciences Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.N.","family":"Srikumar","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology National Institute of Mental Health and Neuro Sciences Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.R.","family":"Raju","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology National Institute of Mental Health and Neuro Sciences Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.S.","family":"Shankaranarayana Rao","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology National Institute of Mental Health and Neuro Sciences Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2004.08.002"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(01)00374-0"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.08.016"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880200903188534"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.5"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.10.018"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2011.07.013"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.08.034"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.08.020"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-2054-x"},{"key":"e_1_2_5_12_1","first-page":"97","volume-title":"Assessment of anxiety and depressive behaviour in animal models of psychiatric disorders","author":"Bhagya V","year":"2012"},{"key":"e_1_2_5_13_1","first-page":"84","volume-title":"Methods of assessment of learning and memory in rodents","author":"Bhagya V","year":"2012"},{"key":"e_1_2_5_14_1","first-page":"66","volume-title":"Estimation of neurotransmitters in the brain by chromatographic methods","author":"Bhagya V","year":"2012"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/026988110201600112"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.100073"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5033-04.2005"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(97)00484-X"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3335-y"},{"key":"e_1_2_5_20_1","first-page":"417","article-title":"The role of the hippocampus in the pathophysiology of major depression","volume":"29","author":"Campbell S","year":"2004","journal-title":"J Psychiatry Neurosci"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2003.10.004"},{"key":"e_1_2_5_22_1","first-page":"49","article-title":"Pre\u2010 and post\u2010training infusion of prazosin into the bed nucleus of the stria terminalis impaired acquisition and retention in a Morris water maze task","volume":"47","author":"Chen HC","year":"2004","journal-title":"Chin J Physiol"},{"key":"e_1_2_5_23_1","first-page":"108","volume-title":"Recording of extra cellular field potentials from the hippocampal slices. In: Shankaranarayana Rao BS","author":"Christofer T","year":"2012"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)02130-7"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(96)00067-8"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245592"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(96)00276-6"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.01.006"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2003.08.018"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106082899"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-200301000-00002"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2014.04.033"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00657-4"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.04.066"},{"key":"e_1_2_5_36_1","doi-asserted-by":"crossref","unstructured":"GovindarajanA Shankaranarayana RaoBS DeeptiN TrinhM MawjeeN TonegawaS ChattarjiS.2006.Transgenic brain\u2010derived neurotrophic factor expression causes both anxiogenic and antidepressant effects.Proc Natl Acad Sci U S A103:13208\u201313213.","DOI":"10.1073\/pnas.0605180103"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(02)01501-9"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-014-9653-0"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00838-3"},{"key":"e_1_2_5_40_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1176\/jnp.16.3.261","article-title":"The role of norepinephrine in the behavioral and psychological symptoms of dementia","volume":"16","author":"Herrmann N","year":"2004","journal-title":"J Neuropsychiatr Clin Neurosci"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.017"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2004.05.026"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(19990301)31:3<196::AID-SYN4>3.0.CO;2-K"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1995.1086"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhm164"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1996.39016.x"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00119-4"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01351.x"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-21-08451.1997"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03756-3"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301527"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1997.00550200046009"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07166.x"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.8.787"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000080648.01911.9a"},{"key":"e_1_2_5_56_1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/S0022-3565(24)29568-9","article-title":"Reboxetine modulates the firing pattern of dopamine cells in the ventral tegmental area and selectively increases dopamine availability in the prefrontal cortex","volume":"297","author":"Linner L","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-003-0084-9"},{"key":"e_1_2_5_58_1","first-page":"77","volume-title":"Assay of acetylcholinesterase activity in the brain","author":"Mahati K","year":"2012"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-24-09104.2000"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.69"},{"key":"e_1_2_5_61_1","first-page":"83","article-title":"Clomipramine modifies fluctuations of forced swimming immobility in different phases of the rat estrous cycle","volume":"27","author":"Marvan ML","year":"1996","journal-title":"Arch Med Res"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145710000908"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219731110"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(00)00164-7"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(01)00546-9"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.02.048"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.09.019"},{"key":"e_1_2_5_68_1","article-title":"Pharmacological and neurobiochemical evidence for antidepressant\u2010like effect of Sumind: a herbal product in animals","author":"Nanjappa KN","year":"2007","journal-title":"Internet J Nutr Wellness 4"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.09.063"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb52363.x"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300661"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.04.006"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(78)90118-8"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01271532"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020050135"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9511-x"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9450.00292"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.0389"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900001358"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300514"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e3282fe8871"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702926"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.03.029"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.122.5.509"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0382-7"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1250-4"},{"key":"e_1_2_5_87_1","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1523\/JNEUROSCI.22-09-03638.2002","article-title":"Overcoming the effects of stress on synaptic plasticity in the intact hippocampus: rapid actions of serotonergic and antidepressant agents","volume":"22","author":"Shakesby AC","year":"2002","journal-title":"J Neurosci"},{"key":"e_1_2_5_88_1","first-page":"115","volume-title":"Recording of extracellular field potential in the hippocampal slices","author":"Shankaranarayana Rao BS","year":"2004"},{"key":"e_1_2_5_89_1","first-page":"112","volume-title":"The brain slice technique","author":"Shankaranarayana Rao BS","year":"2004"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020703901794"},{"key":"e_1_2_5_91_1","first-page":"22","volume-title":"Estimation of neurotransmitters in the rat brain by chromatographic methods","author":"Shankaranarayana Rao BS","year":"2008"},{"key":"e_1_2_5_92_1","first-page":"32","volume-title":"Assay of acetylcholine esterase activity in the discrete regions of the rat brain","author":"Shankaranarayana Rao BS","year":"2008"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.8.1516"},{"key":"e_1_2_5_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.09.008"},{"key":"e_1_2_5_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100791"},{"key":"e_1_2_5_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.10.043"},{"key":"e_1_2_5_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.08.041"},{"key":"e_1_2_5_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0801-4"},{"key":"e_1_2_5_99_1","first-page":"282","article-title":"Chronic oxotremorine treatment reverses stress\u2010induced impairment of hippocampal long\u2010term potentiation and spatial learning in rats","volume":"38","author":"Srikumar BN","year":"2008","journal-title":"Soc Neurosci Abstr"},{"key":"e_1_2_5_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3956(00)00040-6"},{"key":"e_1_2_5_101_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050045"},{"key":"e_1_2_5_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00151-9"},{"key":"e_1_2_5_103_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.049452"},{"key":"e_1_2_5_104_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-0108"},{"key":"e_1_2_5_105_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026606201069"},{"key":"e_1_2_5_106_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300488"},{"key":"e_1_2_5_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001763"},{"key":"e_1_2_5_108_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03851.x"},{"key":"e_1_2_5_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.03.059"},{"key":"e_1_2_5_110_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21907"},{"key":"e_1_2_5_111_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2279-3"},{"key":"e_1_2_5_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(92)90022-8"},{"key":"e_1_2_5_113_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020992314534"},{"key":"e_1_2_5_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(05)80159-9"},{"key":"e_1_2_5_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(05)80164-2"},{"key":"e_1_2_5_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(05)80160-5"},{"key":"e_1_2_5_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(95)02276-7"},{"key":"e_1_2_5_118_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890600610973"},{"key":"e_1_2_5_119_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4426-03.2004"},{"key":"e_1_2_5_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00291-7"},{"key":"e_1_2_5_121_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301052"},{"key":"e_1_2_5_122_1","doi-asserted-by":"publisher","DOI":"10.1038\/387497a0"},{"key":"e_1_2_5_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91773-L"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.23473","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.23473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T09:07:54Z","timestamp":1746349674000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.23473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,21]]},"references-count":122,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/jnr.23473"],"URL":"https:\/\/doi.org\/10.1002\/jnr.23473","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,21]]}}}