title: Estradiol attenuates the cognitive deficits in the novel object recognition task induced by sub-chronic phencyclidine in ovariectomized rats.
abstract: Clinical studies have suggested that estrogens may affect the symptoms of schizophrenia. The novel object recognition task (NORT) in female rats treated with sub-chronic phencyclidine (PCP) was used as an animal model of the cognitive deficits in schizophrenia. The current studies investigated whether chronic estradiol (E) could alleviate sub-chronic PCP-induced cognitive deficits in the NORT. Adult Sprague-Dawley rats were ovariectomized (ovx) and treated with either sub-chronic PCP (2 mg/kg bidaily i.p. for seven days), or with 0.9% saline and their object recognition memory was tested with the NORT using an acquisition trial, 1 min inter-trial interval, and retention trial. Sub-chronic PCP administration did not reliably affect behavior in the acquisition trial but significantly impaired object recognition in the retention trial for 1-2 and 27-29 weeks. Ovx females spent significantly (p<0.05) more time exploring the novel compared to the familiar object, whereas PCP-treated ovx females did not. This effect of PCP was attenuated by long-lasting E capsules implanted prior to PCP treatment. PCP-treated females implanted with E again spent significantly more time exploring the novel compared to the familiar object (p<0.01). When ovx rats were treated with sub-chronic PCP and a long-lasting E capsule was implanted either before or after PCP treatment, estradiol alleviated the PCP-induced deficits when administered in either regimen (p=0.01 and p=0.047 respectively). These data suggest that further exploration of estradiol as a possible therapeutic compound to treat the cognitive deficits of schizophrenia is warranted.
authors.affiliation: Neuroscience, Oberlin College, 119 Woodland Street, Oberlin, OH 44074, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Roseman
authors.forename: Claire
authors.initials: C
authors.lastname: McGregor
authors.forename: Janice E
authors.initials: JE
authors.lastname: Thornton
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D006213:Hallucinogens / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D010052:Ovariectomy; D010622:Phencyclidine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D004967:Estrogens; D006213:Hallucinogens; D004958:Estradiol; D010622:Phencyclidine