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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 168 - 177 (10page)
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초록· 키워드
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Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.
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참고문헌 (44)
참고문헌 신청
Brace H / 1997 / Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus / Brain Res. Bull 43:447~455
Brambilla A / 1996 / Pharmacological characterization of AMPA-induced biting behaviour in mice / Eur. J. Pharmacol 305:115~117
Cahusac PM / 1984 / The behavioural effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats / Neuropharmacology 23:719~724
Cairns BE / 2003 / Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle / J. Neurophysiol 90:2098~2105
Chung KC / 2000 / A systemic administration of NMDA induces immediate early gene pip92 in the hippocampus / J. Neurochem 75:9~17
Brambilla A / 1996 / Pharmacological characterization of AMPA-induced biting behaviour in mice / Eur. J. Pharmacol 305:115~117
Cahusac PM / 1984 / The behavioural effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats / Neuropharmacology 23:719~724
Cairns BE / 2003 / Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle / J. Neurophysiol 90:2098~2105
Chung KC / 2000 / A systemic administration of NMDA induces immediate early gene pip92 in the hippocampus / J. Neurochem 75:9~17
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