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MK-801 suppresses muricidal behavior but not locomotion in olfactory bulbectomized rats: involvement of NMDA
Ying-Jui Ho1, Kuang-Ho Chen, Mei-Yun Tai
1Division of Clinical Psychology, School of Psychology, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
Abstract:
In rats, olfactory bulbectomy (OBX) causes changes in glutamatergic function in the amygdala (AMG) and induces mouse-killing behavior (MKB). The medial AMG (mAMG) plays an important role in the initiation and maintenance of OBX-induced MKB. In the present study, systemic injection or intra-mAMG perfusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) was used to determine the effects of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on the expression of OBX-induced MKB in male Wistar rats that had undergone OBX 1 month previously. The effects of MK-801 on locomotion in OBX rats were also examined using the open-field test. Intraperitoneal injection of MK-801 at doses of 0.10 and 0.15 mg/kg resulted in reversible suppression of MKB, the effect being maximal within 1 h after drug treatment, then gradually disappearing over 6 h. Locomotor distance in OBX rats was not affected using 0.10 mg/kg of MK-801, but increased after treatment with 0.15 mg/kg of MK-801; both doses, however, caused the rats to spend longer in the central area of the open field. MKB was also reversibly suppressed by local perfusion of 1 mM MK-801 at a rate of 1 microl/min into the mAMG through microdialysis probes. These results suggest that NMDA receptors, at least, in the mAMG, are involved in the expression of OBX-induced MKB.
Insights
Olfactory bulbectomy in rats induces mouse-killing behavior, which is suppressed by the NMDA receptor antagonist MK-801. This suggests N-methyl-d-aspartate receptors in the medial amygdala are crucial for this behavior.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Pharmacology
Background:
- Olfactory bulbectomy (OBX) in rats alters glutamatergic function in the amygdala (AMG), leading to mouse-killing behavior (MKB).
- The medial amygdala (mAMG) is critical for the development and persistence of OBX-induced MKB.
Purpose of the Study:
- To investigate the role of N-methyl-d-aspartate (NMDA) receptors in the expression of OBX-induced MKB.
- To examine the effects of the NMDA receptor antagonist MK-801 on MKB and locomotion in OBX rats.
Main Methods:
- Systemic administration and local microdialysis perfusion of MK-801 in male Wistar rats previously subjected to OBX.
- Assessment of MKB and locomotor activity using the open-field test.
Main Results:
- Systemic MK-801 (0.10 and 0.15 mg/kg) reversibly suppressed MKB, with effects diminishing over 6 hours.
- Locomotion was unaffected at 0.10 mg/kg but increased at 0.15 mg/kg; both doses increased time spent in the central open-field area.
- Local perfusion of MK-801 into the mAMG also reversibly suppressed MKB.
Conclusions:
- NMDA receptors in the medial amygdala are implicated in the expression of olfactory bulbectomy-induced mouse-killing behavior.
- Targeting NMDA receptor function may offer a therapeutic strategy for related behavioral changes.
