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.