Sex differences in NMDA receptor mediated responses in rats

The behavioural effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) were compared in age-matched female and male Wistar rats. At a dose of 0.1 mg/kg i.p., almost no behavioural alterations were seen in male rats, while marked and long-lasting phencyclidine-like behavioural alterations, such as ataxia, hyperlocomotion, and head weaving were observed in female rats. When the dosage of MK-801 was increased to 0.3 mg/kg, these behavioural alterations were also observed in male animals, but with lower intensity and/or duration than in female rats. The data demonstrate that female rats are much more susceptible to NMDA receptor blockade than males, suggesting sex related differences in the endogenous modulation of this glutamate subreceptor.