Excessive cerebrocortical release of acetylcholine induced by NMDA antagonists is reduced by GABAergic and alpha(2)-adrenergic agonists
- Authors
- Kim, SH; Price, MT; Olney, JW; Farber, NB
- Issue Date
- Jul-1999
- Publisher
- STOCKTON PRESS
- Keywords
- NMDA antagonists; schizophrenia; Alzheimer's disease; posterior cingulate; retrosplenial cortex; MK-801; ketamine; microdialysis; neurotoxicity
- Citation
- MOLECULAR PSYCHIATRY, v.4, no.4, pp 344 - 352
- Pages
- 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR PSYCHIATRY
- Volume
- 4
- Number
- 4
- Start Page
- 344
- End Page
- 352
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/23894
- DOI
- 10.1038/sj.mp.4000529
- ISSN
- 1359-4184
1476-5578
- Abstract
- N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor antagonists (eg MK-801, ketamine, phencyclidine [PCP]) injure cerebrocortical neurons in the posterior cingulate and retrosplenial cortex (PC/RSC). We have proposed that the neurotoxic action of these agents is mediated in part by a complex polysynaptic mechanism involving an interference in GABAergic inhibition resulting in excessive release of acetylcholine (ACh). Previously we have found that the systemic injection of GABAergic agents and alpha(2)-adrenergic agonists can block this neurotoxicity. In the present study we tested the hypothesis that NMDA antagonists trigger release of ACh in PC/RSC and that this action of NMDA antagonists is suppressed by GABAergic agents or alpha(2)-adrenergic agonists. The effect of MK-801 and ketamine on PC/RSC ACh output (and the ability of pentobarbital, diazepam and clonidine to modify MK-801-induced ACh release) was studied in adult female rats using in vivo microdialysis. Both MK-801 and ketamine caused a significant rise in PC/RSC ACh output compared to basal levels. Pentobarbital, diazepam and clonidine suppressed MK-801's effect on ACh release. Exploratory studies indicated that the site of action of these agents was outside of the PC/RSC. The microdialysis results are consistent with several aspects of the circuitry proposed to mediate the neurotoxic action of NMDA antagonists.
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- Appears in
Collections - 2. Clinical Science > Department of Psychiatry > 1. Journal Articles
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