The effect of anosmia on MK-801-induced behaviour in mice.
Systemic administration of N-methyl-D-aspartate (NMDA) receptor antagonists induces a well defined behaviour in rodents characterized by, for example increased locomotion and ataxia. It is not clear in what brain region(s) NMDA antagonists induce this behaviour. We have studied the possible involvement of olfactory pathways by making adult mice anosmic via intranasal injection of zinc sulphate, a procedure that is known to destroy the olfactory epithelium. The NMDA antagonist MK-801 was given intraperitoneally (0.1-1.0 mg/kg) and the animals were scored for locomotion and ataxia 60-90 min later. Before MK-801 administration, olfactory-lesioned mice did not differ from non-lesioned controls with regard to locomotion or ataxia. MK-801 caused locomotor activation (> or = 0.2 mg/kg) and ataxia (> or = 0.5 mg/kg) in both groups. In general, olfactory-lesioned animals showed more locomotion and less ataxia after MK-801 administration than non-lesioned animals. Lesioned animals displayed 2.0- (P < 0.05) and 3.7-fold (P < 0.05) more extensive locomotor activation than non-lesioned animals after 0.5 and 1.0 mg/kg of MK-801, respectively. No difference 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 of ataxia after 1.0 mg/kg of MK-801, indicating that the enhanced MK-801-induced locomotor activation in olfactory-lesioned mice was not simply due to less ataxia. These results suggest that olfactory input is involved in NMDA antagonist-induced behaviour.
Andiné
P
P
Department of Psychiatry, Sahlgrenska University Hospital, Sweden.
Axelsson
R
R
Jacobson
I
I
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003714:Denervation; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D000857:Olfaction Disorders / Q000139:chemically induced / Q000523:psychology*; D009830:Olfactory Bulb / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D013431:Sulfates; D017967:Zinc Compounds; D019287:Zinc Sulfate
D018846:Excitatory Amino Acids; D013431:Sulfates; D017967:Zinc Compounds; D016291:Dizocilpine Maleate; D019287:Zinc Sulfate