Inhibitors of kynurenine 3-hydroxylase have previously been used to increase endogenous levels of kynurenic acid, an excitatory amino acid receptor antagonist. In the present electrophysiological study PNU 156561A was utilized to elevate endogenous concentrations of kynurenic acid and subsequent effects on the firing pattern of dopamine (DA) neurons of rat substantia nigra (SN) were analyzed. Pretreatment with PNU 156561A (40 mg/kg, i.v., 5–7 h) caused a five-fold increase in endogenous kynurenic acid levels in whole brain five to seven hours after administration and also evoked a significant increase in firing rate and bursting activity of nigral DA neurons. The results of the present study show that a moderate increase in endogenous kynurenic acid levels produces significant actions on the tonic glutamatergic control of the firing pattern of nigral DA neurons, and implicate kynurenine 3-hydroxylase inhibitors as novel antiparkinsonian agents.
This is a preview of subscription content, log in via an institution to check access.
Access this article Subscribe and saveSpringer+ Basic
€34.99 /Month
Price includes VAT (Germany)
Instant access to the full article PDF.
Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. Author information Authors and AffiliationsDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden, , , , , , SE
S. Erhardt, H. Öberg, J. M. Mathé & G. Engberg
Received April 3, 2000 Accepted July 2, 2000
About this article Cite this articleErhardt, S., Öberg, H., Mathé, J. et al. Pharmacological elevation of endogenous kynurenic acid levels activates nigral dopamine neurons. Amino Acids 20, 353–362 (2001). https://doi.org/10.1007/s007260170032
Issue Date: June 2001
DOI: https://doi.org/10.1007/s007260170032
RetroSearch is an open source project built by @garambo | Open a GitHub Issue
Search and Browse the WWW like it's 1997 | Search results from DuckDuckGo
HTML:
3.2
| Encoding:
UTF-8
| Version:
0.7.4