MK-801 produces a reduction in anxiety-related antipredator defensiveness in male and female rats and a gender-dependent increase in locomotor behavior

The present study investigated the effects of the non-competitive NMDA antagonist MK-801 (0.04–0.16 mg/kg), on antipredator defensive reactions of male and female rats in three paradigms comprising the Anxiety/Defense Test Battery (A/DTB). In order to facilitate interpretation of data from the above study, the behavioral effects of the compound were also assessed in the non-threatening environment of the home cage. The data indicate a marked gender difference in the locomotor effects of the compound with females, but not males, showing a dose-dependent increase in general locomotor activity, a decrease in freezing, and a loss of balance at the highest dose, in both non-threatening and threatening contexts. The behavioral profile for males in the A/DTB included decreased orientation to and proxemic avoidance of the cat stimulus or stimulus site, and increased transits and eating in the cat situation. Contacts with the cat odor stimulus were increased, as was normal, curved back, locomotion in this test. In the absence of non-specific locomotor effects for males, this profile for the A/DTB provides convincing evidence for anxiety/fear reduction with MK-801. While locomotor effects tended to mask the putative anxiolytic properties of the compound in females, evidence remains from behavioral changes not attributable to a locomotor influence to indicate anxiety/fear reduction in this sex.Supported by NIH Grants MH42803 and RR03061