Estradiol attenuates the cognitive deficits in the novel object recognition task induced by sub-chronic phencyclidine in ovariectomized rats

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.

► Estradiol reversed the long-lasting deficit in novel object recognition induced by sub-chronic PCP administration.
► Estradiol reversed the deficit in object recognition when implanted either before or after sub-chronic PCP administration.
► With a short inter-trial interval both ovx and ovx, estradiol-treated females showed object recognition.
► Sub-chronic PCP administration produced deficits in object recognition for up to 27–29 weeks.