Effect of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on food-anticipatory activity rhythm in the rat.
When feeding was restricted to a single meal scheduled at a fixed time (1300-1700 h) in the day, rats exhibited increased prefeeding locomotor activity 1-3 h before the feeding time, which increased over 6 days. The activity increase was seen for about 5 h (1100-1600 h) on the seventh day when no food was provided (fasting day), as the rat anticipated mealtime. Thus, mealtime-associated activity rhythm on the fasting day was considered to be another good index of food-anticipatory activity. In this study, we investigated the effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, which has been reported to cause impairment of spatial learning, on food-anticipatory activity in rats. Daily injection of MK-801 (0.2 mg/kg) at 1700 h for 6 successive days impaired the development of increased prefeeding activity. The appearance of mealtime-associated activity was impaired by daily injection of MK-801 (0.2 mg/kg) at 1700 h (immediately after food restriction, FR) or at 1900 h (2 h after FR) but not at 0900 (16 h after FR). In addition, mealtime-associated activity was impaired by MK-801 injected at 1700 h in a dose-dependent manner (0.1-1 mg/kg). The present results demonstrate that NMDA receptor mechanisms were involved in learning processes of food anticipation and suggest that an impairment of food-anticipatory activity may be considered an animal model of a deficit of "temporal learning".
Ono
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Shibata
S
S
Minamoto
Y
Y
Watanabe
S
S
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D006220:Haloperidol