PMID- 25315361 OWN - NLM STAT- MEDLINE DCOM- 20150902 LR - 20211021 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 232 IP - 6 DP - 2015 Mar TI - Behavioral effects of nicotinic antagonist mecamylamine in a rat model of depression: prefrontal cortex level of BDNF protein and monoaminergic neurotransmitters. PG - 1095-105 LID - 10.1007/s00213-014-3745-5 [doi] AB - Several studies have pointed to the nicotinic acetylcholine receptor (nAChR) antagonists, such as mecamylamine (MEC), as a potential therapeutic target for the treatment of depression. The present study evaluated the behavioral and neurochemical effects of chronic administration of MEC (1, 2, and 4 mg/kg/day, intraperitoneally (i.p.)) in Wistar rats exposed to chronic restraint stress (CRS, 4 h x 6 W). MEC prevented CRS-induced depressive-like behavior via increasing sucrose preference, body weight, and forced swim test (FST) struggling and swimming while reducing immobility in FST and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity (adrenal gland weight and serum corticosterone). At the same time, MEC amended CRS-induced anxiety as indicated by decreasing central zone duration in open field test and increasing active interaction duration. Additionally, MEC modulated the prefrontal cortex (PFC) level of brain-derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), and norepinephrine (NE). In conclusion, the present data suggest that MEC possesses antidepressant and anxiolytic-like activities in rats exposed to CRS. These behavioral effects may be in part mediated by reducing HPA axis hyperactivity and increasing PFC level of BDNF and monoamines. Accordingly, these findings further support the hypothesis that nAChRs blockade might afford a novel promising strategy for pharmacotherapy of depression. FAU - Aboul-Fotouh, Sawsan AU - Aboul-Fotouh S AD - Department of Pharmacology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt, 11566, sawsanaf2005@yahoo.com. LA - eng PT - Journal Article DEP - 20141015 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nicotinic Antagonists) RN - 333DO1RDJY (Serotonin) RN - 6EE945D3OK (Mecamylamine) RN - W980KJ009P (Corticosterone) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Behavior, Animal/*drug effects MH - Body Weight/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Corticosterone MH - Depressive Disorder/*metabolism MH - Disease Models, Animal MH - Hypothalamo-Hypophyseal System/drug effects/metabolism MH - Mecamylamine/*pharmacology MH - Nicotinic Antagonists/*pharmacology MH - Norepinephrine/*metabolism MH - Pituitary-Adrenal System/drug effects/metabolism MH - Prefrontal Cortex/*drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Restraint, Physical MH - Serotonin/*metabolism MH - Stress, Psychological/metabolism MH - Swimming EDAT- 2014/10/16 06:00 MHDA- 2015/09/04 06:00 CRDT- 2014/10/16 06:00 PHST- 2014/07/23 00:00 [received] PHST- 2014/09/10 00:00 [accepted] PHST- 2014/10/16 06:00 [entrez] PHST- 2014/10/16 06:00 [pubmed] PHST- 2015/09/04 06:00 [medline] AID - 10.1007/s00213-014-3745-5 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2015 Mar;232(6):1095-105. doi: 10.1007/s00213-014-3745-5. Epub 2014 Oct 15.