Anxiolytic-like effects of the noncompetitive NMDA antagonist MK 801

The present study examined the effects of the noncompetitive NMDA antagonist, MK 801 (dizocilpine), on behavior in the conditioned suppression of drinking (CSD) punished drinking paradigm, a repeated-measures conflict task. In daily 10- or 15-min sessions, water-restricted rats drank from a tube that was occasionally electrified (0.25- or 0.5-mA shocks signaled by a tone). Trained subjects (4 weeks of CSD testing) exhibited stable baselines for both punished (approximately 40 or 100 shocks received/session at the 0.5- and 0.25-mA shock intensities, respectively) and unpunished (approximately 15 ml/session water intake at either shock intensity) responding. Over a wide range of doses, (+) MK 801 did not increase punished responding when administered using a 10-min, 4-h, or 48-h pretreatment. However, at a 24-h pretreatment (+) MK 801 (0.04-0.4 mg/kg, IP) produced a dramatic and dose-dependent increase in punished responding. The "inactive" (-) isomer of MK 801 did not produce a significant anxiolytic-like effect in the CSD paradigm at doses up to 2 mg/kg when tested using a 24-h pretreatment. These data suggest that the anticonvulsant agent (+) MK 801 also may exert antianxiety effects in humans.