THE EFFECT OF ANOSMIA ON MK-801-INDUCED BEHAVIOR IN MICE

Systemic administration of N-methyl-D-aspartate (NMDA) receptor antago nists induces a well defined behaviour in rodents characterized by, fo r example increased locomotion acid ataxia. It is not clear in what br ain region(s) NMDA antagonists induce this behaviour. We have studied the possible involvement of olfactory pathways by making adult mice an osmic via intranasal injection of zinc sulphate, a procedure that is k nown to destroy the olfactory epithelium. The NMDA antagonist MK-801 w as given intraperitoneally (0.1-1.0 mg/kg) and the animals were scored for locomotion and ataxia 60-90 min later. Before MK-801 administrati on, olfactory-lesioned mice did not differ from non-lesioned controls with regard to locomotion or ataxia. MK-801 caused locomotor activatio n (greater than or equal to 0.2 mg/kg) and ataxia (greater than or equ al to 0.5 mg/kg) in both groups. In general, olfactory-lesioned animal s showed more locomotion and less ataxia after MK-801 administration t han non-lesioned animals. Lesioned animals displayed 2.0- (P < 0.05) a nd 3.7-fold (P < 0.05) more extensive locomotor activation than non-le sioned animals after 0.5 and 1.0 mg/kg of MK-801, respectively, No dif ference in the degree of ataxia was seen between the two groups at 0.5 mg/kg, whereas non-lesioned animals showed a 2.1-fold higher degree o f ataxia after 1.0 mg/kg of MK-801, indicating that the enhanced MK-80 1-induced locomotor activation in olfactory-lesioned mice was not simp ly due to less ataxia. These results suggest that olfactory input is i nvolved in NMDA antagonist-induced behaviour.