Anticonflict effect of MK-801 in rats: Time course and chronic treatment studies

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1995-08, Vol.51 (4), p.635-640
• Main Authors: Xie, Zhongcong C., Buckner, Erica, Commissaris, Randall L.
• Format: Article
• Language: English
• Subjects: Animals; Anxiolytics; Behavior, Animal - drug effects; Biological and medical sciences; Chronic treatment; Conditioning, Operant - drug effects; Conflict (Psychology); Conflict behavior; Dizocilpine Maleate - pharmacology; Drinking Behavior - drug effects; Electroshock; Female; Male; Medical sciences; MK-801; Neuropharmacology; NMDA receptor complex; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Sex Characteristics; Sex differences; Time course; Time Factors
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(94)00428-L

The present study examined the time course and chronic treatment effects of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801 (dizocilpine), on conflict behavior in the conditioned suppression of drinking (CSD) paradigm, a repeated-measures conflict task. In daily 10-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 responding and unpunished responding. In the first experiment, the effects of MK-801 administered IP were determined in female and male rats following a range of pretreatment intervals (i.e., 0.5–48 h). In female rats, 0.2 mg/kg MK-801 exerted an anticonflict effect at pretreatment intervals of 10–36 h, but not before 10 h or after 36 h. In male rats, qualitatively similar results were obtained; MK-801 (0.4 mg/kg) exerted anticonflict effects following pretreatment intervals of 6–14 h, but not before 6 or after 14 h. In the second experiment, chronic treatment of female rats with 0.04, 0.1, or 0.2 mg/kg MK-801 resulted in a dose-dependent anticonflict effect in CSD paradigm, which remained stable over the course of 5 weeks of chronic treatment. Punished responding returned to pretreatment levels within 2–3 days after discontinuation of chronic treatment with MK-801. These data suggest that MK-801 exerts a delayed anticonflict effect in both female and male rats with a qualitatively similar pattern, and that there is no tolerance to the anticonflict effect of MK-801 with chronic treatment.