title: Environmental enrichment has antidepressant-like action without improving learning and memory deficits in olfactory bulbectomized rats.
abstract: Depression, especially in the elderly, is associated with poor cognitive functioning. Exercise has received much attention in the treatment for depression and also dementia. Here we studied the effect of an enriched environment combined with voluntary exercise (EE/VE) on the olfactory bulbectomized (OBX) rat. The OBX rat is hyperactive in an open field, which is normalized by chronic antidepressant treatment, and suffers from learning and memory impairments. Neurotrophic factors are thought to be involved in the antidepressant action of EE/VE. Hyperactivity and cognitive functioning (both hippocampal dependent and independent tasks) were investigated before and after EE/VE. We quantified hippocampal mRNA levels of the neurotrophic factors BDNF, VGF and VEGF. VEGF receptor (FLK-1) inhibition was achieved by i.c.v administration of the antagonist SU5416 during the period of EE/VE. OBX almost completely blocked fear memory acquired either 48 h or 28 days before surgery. EE/EV normalized OBX-induced hyperactivity in open field, while having no effect on the decrease in hippocampal dependent learning and memory. VEGF mRNA levels in hippocampus were significantly increased both in OBX and control rats following EE/VE. OBX reduced BDNF mRNA levels, but EE did not reverse this. Inhibition of the FLK-1 receptor did not suppress EE/VE induced normalization of the hyperactivity of the OBX rat. The lack of effect of EE/VE on cognitive parameters, while normalizing hyperactivity, suggests different neuronal mechanisms underlying OBX-induced behavioral changes. Since EE/VE still normalizes the OBX-induced hyperactivity while the FLK-1 receptor was blocked, we assume that VEGF is not obligatory for the antidepressant effect of EE/VE. This article is part of a Special Issue entitled 'Anxiety and Depression'.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. h.hendriksen@uu.nl
authors.forename: Hendrikus
authors.initials: H
authors.lastname: Hendriksen
authors.forename: Didier
authors.initials: D
authors.lastname: Meulendijks
authors.forename: Tessa N
authors.initials: TN
authors.lastname: Douma
authors.forename: Diewertje I
authors.initials: DI
authors.lastname: Bink
authors.forename: Megan E
authors.initials: ME
authors.lastname: Breuer
authors.forename: Koen G C
authors.initials: KG
authors.lastname: Westphal
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000628:therapy*; D004195:Disease Models, Animal; D004777:Environment; D005081:Exercise Therapy; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007859:Learning Disabilities / Q000209:etiology / Q000628:therapy*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000628:therapy*; D009830:Olfactory Bulb / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000502:physiology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C116890:Semaxinib