Artikel
Lesions of the entopeduncular nucleus in rats worsen the disruptive effects of the NMDA receptor antagonist MK 801 on sensorimotor gating
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Autoren
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G. Lütjens
- Klinik für Neurochirurgie, Medizinische Hochschule Hannover; Zentrum für Systemische Neurowissenschaften
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J.K. Krauss
- Klinik für Neurochirurgie, Medizinische Hochschule Hannover; Zentrum für Systemische Neurowissenschaften
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K. Schwabe
- Klinik für Neurochirurgie, Medizinische Hochschule Hannover; Zentrum für Systemische Neurowissenschaften
| Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Sensorimotor gating is disturbed in certain neuropsychiatric disorders with known or proposed abnormalities of basal ganglia function such as schizophrenia, obsessive compulsive disorder and Tourette's syndrome. Prepulse inhibition (PPI) of the acoustic startle reaction is an operational measure of sensorimotor gating, and PPI deficits induced by NMDA receptor antagonists serve as an animal model for neuropsychiatric symptoms. Little is known, however, about the role of the entopeduncular nucleus (EPN, i.e., the rat equivalent to the human globus pallidus internus) in pharmacologically induced PPI deficits although the EPN is an important output structure of the basal ganglia and its human equivalent used in functional neurosurgery.
Methods: In male Sprague Dawley rats bilateral EPN lesions were induced by stereotaxic injection of ibotenate (4 µg in 0.4 µl; n=11) or sham-lesions by injection of a vehicle (n=7). Rats were then tested for PPI of ASR in a startle response system and for locomotor activity in an open field after subcutaneous injection of the NMDA receptor antagonist MK801 (0.0 mg/kg and 0.15 mg/kg).
Results: EPN lesions did not affect baseline PPI but worsened the PPI-disruptive effect of MK801 in lesioned compared to sham-lesioned rats (two-way ANOVA with post-hoc Tukey's test, p < 0.05). Locomotor activity was significantly higher after drug injection in both sham-lesioned and lesioned rats (p < 0.05) without a difference between the two groups.
Conclusions: These data suggest that the EPN is an important brain region within the neuronal circuit responsible for NMDA receptor antagonist-induced deficient sensorimotor gating.
