PMID- 22634064 OWN - NLM STAT- MEDLINE DCOM- 20121119 LR - 20181201 IS - 1873-5177 (Electronic) IS - 0091-3057 (Linking) VI - 102 IP - 2 DP - 2012 Aug TI - Antidepressant-like effects of Delta(9)-tetrahydrocannabinol and rimonabant in the olfactory bulbectomised rat model of depression. PG - 357-65 LID - 10.1016/j.pbb.2012.05.009 [doi] AB - The endocannabinoid signalling system is widely accepted to play a role in controlling the affective state. Plant cannabinoids are well known to have behavioural effects in animals and humans and the cannabinoid CB(1) receptor antagonist rimonabant has recently been shown to precipitate depression-like symptoms in clinical trial subjects. The aim of the present study was to investigate the behavioural and neurochemical effects of chronic administration of Delta(9)-tetrahydrocannabinol (THC) and rimonabant on intact and olfactory bulbectomised (OB) rats used as a model of depression. As expected, OB rats were hyperactive in the open field. Repeated THC (2 mg/kg, i.p. once every 48 h for 21 days) and rimonabant (5 mg/kg, i.p. once every 48 h for 21 days) reduced this hyperactivity, which is typical of clinically effective antidepressant drugs. In intact animals, chronic THC increased brain derived neurotrophic factor (BDNF) expression levels in the hippocampus and frontal cortex but rimonabant had no effect. Rimonabant increased the levels of phosphorylated extracellular signal regulated kinases (p-ERKs(1/2)) in the hippocampus and prefrontal cortex and THC also increased expression in frontal cortex. OB did not affect BDNF or p-ERK(1/2) expression in the hippocampus or frontal cortex and in, contrast to the intact animals, neither THC nor rimonabant altered expression in the OB rats. These findings indicate antidepressant-like behavioural properties of both THC and rimonabant in OB rats although additional studies are required to clarify the relationship between the chronic effects of cannabinoids in other pre-clinical models and in human depression. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Elbatsh, Maha M AU - Elbatsh MM AD - School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. maha.ali@med.menofia.edu.eg FAU - Moklas, M A A AU - Moklas MA FAU - Marsden, C A AU - Marsden CA FAU - Kendall, D A AU - Kendall DA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120524 PL - United States TA - Pharmacol Biochem Behav JT - Pharmacology, biochemistry, and behavior JID - 0367050 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cannabinoid Receptor Antagonists) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 7J8897W37S (Dronabinol) RN - RML78EN3XE (Rimonabant) SB - IM MH - Animals MH - Antidepressive Agents/*therapeutic use MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cannabinoid Receptor Antagonists MH - Depression/*drug therapy MH - *Disease Models, Animal MH - Dronabinol/*therapeutic use MH - Frontal Lobe/enzymology/metabolism MH - Hippocampus/enzymology/metabolism MH - MAP Kinase Signaling System MH - Male MH - Olfactory Bulb/*surgery MH - Piperidines/*therapeutic use MH - Pyrazoles/*therapeutic use MH - Rats MH - Rimonabant EDAT- 2012/05/29 06:00 MHDA- 2012/12/10 06:00 CRDT- 2012/05/29 06:00 PHST- 2011/11/21 00:00 [received] PHST- 2012/05/08 00:00 [revised] PHST- 2012/05/19 00:00 [accepted] PHST- 2012/05/29 06:00 [entrez] PHST- 2012/05/29 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] AID - S0091-3057(12)00144-X [pii] AID - 10.1016/j.pbb.2012.05.009 [doi] PST - ppublish SO - Pharmacol Biochem Behav. 2012 Aug;102(2):357-65. doi: 10.1016/j.pbb.2012.05.009. Epub 2012 May 24.