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Oestradiol attenuates the cognitive deficit induced by acute phencyclidine treatment in mature female hooded-Lister rats

JS Sutcliffe

School of Pharmacy, University of Bradford, Bradford, West Yorkshire, UK

F. Rhaman

Leeds University Medical School, University of Leeds, Leeds, West Yorkshire, UK

KM Marshall

School of Pharmacy, University of Bradford, Bradford, West Yorkshire, UK

JC Neill

School of Pharmacy, University of Bradford, Bradford, West Yorkshire, UK, j.c.neill{at}bradford.ac.uk

Gender differences in psychiatric research are becoming more widely recognized, and changes in levels of the steroid hormone, oestrogen, over the menstrual or oestrous cycle are becoming increasingly implicated in alterations in cognitive strategies and capacities. The aim of this study is to investigate the interaction between oestrogen, NMDA receptor function and cognitive processing in rats. Forty-five mature female hooded-Lister rats received vehicle, 0.5, 5 or 10 µg/kg of oestradiol benzoate (EB, s.c. in olive oil) 24 h prior to an acute dose of 2 mg/kg phencyclidine (PCP, i.p. in 0.9% w/v saline), or vehicle (0.9% saline). After 30 min following PCP treatment, animals completed the novel object recognition task with a 1 min inter-trial interval to assess object recognition memory. Results show that 5 and 10 µg/kg of EB 24 h prior to 2 mg/kg PCP significantly (P < 0.01 and < 0.001, respectively) protected against the cognitive impairing effect of PCP in contrast to vehicle and 0.5 µg/kg EB plus PCP (not significant). EB may exert a neuromodulatory effect in this animal model leading to attenuation of the PCP-induced impairment in object recognition memory, suggesting an interaction between the gonadal steroids and NMDA receptor-mediated cognitive dysfunction, which is of potential relevance to schizophrenia.

Key Words: novel object recognition • oestrogen • phencyclidine—PCP • rat • neuroprotection • NMDA receptors • schizophrenia

This version was published on November 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 8, 918-922 (2008)
DOI: 10.1177/0269881107083839
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