PMID- 22695046 OWN - NLM STAT- MEDLINE DCOM- 20131227 LR - 20161125 IS - 1469-5111 (Electronic) IS - 1461-1457 (Linking) VI - 16 IP - 4 DP - 2013 May TI - Behavioural and neurochemical changes induced by stress-related conditions are counteracted by the neurokinin-2 receptor antagonist saredutant. PG - 813-23 LID - 10.1017/S1461145712000612 [doi] AB - These experiments were undertaken to assess the mechanisms underlying the antidepressant-like effects of the neurokinin-2 (NK(2)) receptor antagonist saredutant (SR48968) in rats tested in the forced swim test (FST), by analysing hippocampal brain-derived neurotrophic factor (BDNF) and plasma corticosterone [as index of hypothalamic-pituitary-adrenal (HPA) axis activity]. Male Wistar rats received three intraperitoneal injections over 24 h of vehicle, saredutant (5 mg/kg), citalopram (15 mg/kg), clomipramine (50 mg/kg). Rats were subjected to restraint stress (4 h) 24 h prior to the FST procedure. This stress procedure increased immobility and decreased swimming behaviour in the FST; furthermore, it lowered hippocampal BDNF protein expression and increased plasma corticosterone levels. Saredutant and clomipramine or citalopram, used here as positive controls, reduced the immobility time in the FST both under basal conditions and after stress exposure. This effect was not attributable to changes in locomotion, because locomotor activity was unchanged when assessed in the open field test. Pretreatment with para-cholorophenylalanine (150 mg/kg, 72 h and 48 h prior to FST) abolished the effect of citalopram and saredutant on immobility time. At neurochemical level, saredutant attenuated activation of HPA axis in stressed animals more than clomipramine or citalopram. The behavioural effects of saredutant support the hypothesis that NK(2) receptor activity is involved in stress-related disorders. These effects of saredutant may be related to normalization of the HPA axis. Moreover, saredutant increases BDNF expression in the hippocampus, confirming the role of NK(2) receptor blockade in BDNF activation following stressor application. FAU - Tamburella, Alessandra AU - Tamburella A AD - Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, Catania University, Catania, Italy. FAU - Leggio, Gian Marco AU - Leggio GM FAU - Micale, Vincenzo AU - Micale V FAU - Navarria, Andrea AU - Navarria A FAU - Bucolo, Claudio AU - Bucolo C FAU - Cicirata, Valentina AU - Cicirata V FAU - Drago, Filippo AU - Drago F FAU - Salomone, Salvatore AU - Salomone S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120614 PL - England TA - Int J Neuropsychopharmacol JT - The international journal of neuropsychopharmacology JID - 9815893 RN - 0 (Antidepressive Agents) RN - 0 (Benzamides) RN - 0 (Piperidines) RN - 0 (Receptors, Neurokinin-2) RN - 720U2QK8I5 (SR 48968) SB - IM MH - Animals MH - Antidepressive Agents/pharmacology/*therapeutic use MH - Benzamides/pharmacology/*therapeutic use MH - Hippocampus/chemistry/*drug effects/metabolism MH - Hypothalamo-Hypophyseal System/drug effects/metabolism MH - Male MH - Motor Activity/*drug effects/physiology MH - Piperidines/pharmacology/*therapeutic use MH - Pituitary-Adrenal System/drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Neurokinin-2/*antagonists & inhibitors/metabolism MH - Stress, Psychological/metabolism/*prevention & control EDAT- 2012/06/15 06:00 MHDA- 2013/12/29 06:00 CRDT- 2012/06/15 06:00 PHST- 2012/06/15 06:00 [entrez] PHST- 2012/06/15 06:00 [pubmed] PHST- 2013/12/29 06:00 [medline] AID - S1461145712000612 [pii] AID - 10.1017/S1461145712000612 [doi] PST - ppublish SO - Int J Neuropsychopharmacol. 2013 May;16(4):813-23. doi: 10.1017/S1461145712000612. Epub 2012 Jun 14.