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The effect of anosmia on MK-801-induced behaviour in mice
P Andiné1, R Axelsson, I Jacobson
1Department of Psychiatry, Sahlgrenska University Hospital, Sweden.
Abstract:
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.
Insights
Olfactory pathways influence N-methyl-D-aspartate (NMDA) antagonist-induced behaviors in mice. Removing olfactory input enhanced MK-801
Area of Science:
- Neuroscience
- Behavioral Pharmacology
Background:
- N-methyl-D-aspartate (NMDA) receptor antagonists cause distinct behaviors in rodents, including increased locomotion and ataxia.
- The specific brain regions responsible for these NMDA antagonist-induced behaviors are not fully understood.
Purpose of the Study:
- To investigate the potential involvement of olfactory pathways in NMDA antagonist-induced behaviors.
- To determine if olfactory input modulates the effects of NMDA antagonists like MK-801.
Main Methods:
- Adult mice were rendered anosmic using intranasal zinc sulphate to ablate the olfactory epithelium.
- An NMDA antagonist, MK-801, was administered intraperitoneally at varying doses (0.1-1.0 mg/kg).
- Locomotion and ataxia were assessed 60-90 minutes post-administration in both olfactory-lesioned and control mice.
Main Results:
- Olfactory-lesioned mice showed significantly enhanced locomotor activation compared to non-lesioned controls after MK-801 administration (2.0-fold at 0.5 mg/kg, 3.7-fold at 1.0 mg/kg).
- While ataxia was observed in both groups, olfactory-lesioned mice exhibited less ataxia at higher MK-801 doses.
- The enhanced locomotion in lesioned animals was not solely attributable to reduced ataxia.
Conclusions:
- Olfactory input plays a significant role in modulating NMDA antagonist-induced behaviors.
- These findings suggest that olfactory pathways are involved in the neural circuits underlying NMDA antagonist effects.