title: Phencyclidine (PCP)-induced disruption in cognitive performance is gender-specific and associated with a reduction in brain-derived neurotrophic factor (BDNF) in specific regions of the female rat brain.
abstract: Phencyclidine (PCP), used to mimic certain aspects of schizophrenia, induces sexually dimorphic, cognitive deficits in rats. In this study, the effects of sub-chronic PCP on expression of brain-derived neurotrophic factor (BDNF), a neurotrophic factor implicated in the pathogenesis of schizophrenia, have been evaluated in male and female rats. Male and female hooded-Lister rats received vehicle or PCP (n=8 per group; 2 mg/kg i.p. twice daily for 7 days) and were tested in the attentional set shifting task prior to being sacrificed (6 weeks post-treatment). Levels of BDNF mRNA were measured in specific brain regions using in situ hybridisation. Male rats were less sensitive to PCP-induced deficits in the extra-dimensional shift stage of the attentional set shifting task compared to female rats. Quantitative analysis of brain regions demonstrated reduced BDNF levels in the medial prefrontal cortex (p<0.05), motor cortex (p<0.01), orbital cortex (p<0.01), olfactory bulb (p<0.05), retrosplenial cortex (p<0.001), frontal cortex (p<0.01), parietal cortex (p<0.01), CA1 (p<0.05) and polymorphic layer of dentate gyrus (p<0.05) of the hippocampus and the central (p<0.01), lateral (p<0.05) and basolateral (p<0.05) regions of the amygdaloid nucleus in female PCP-treated rats compared with controls. In contrast, BDNF was significantly reduced only in the orbital cortex and central amygdaloid region of male rats (p<0.05). Results suggest that blockade of NMDA receptors by sub-chronic PCP administration has a long-lasting down-regulatory effect on BDNF mRNA expression in the female rat brain which may underlie some of the behavioural deficits observed post PCP administration.
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4540, USA. ssnigdha@uci.edu
authors.forename: Shikha
authors.initials: S
authors.lastname: Snigdha
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Neill
authors.forename: Samantha L
authors.initials: SL
authors.lastname: McLean
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Shemar
authors.forename: Leonie
authors.initials: L
authors.lastname: Cruise
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shahid
authors.forename: Brian
authors.initials: B
authors.lastname: Henry
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D009483:Neuropsychological Tests; D010622:Phencyclidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; D012333:RNA, Messenger; D010622:Phencyclidine