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Quinolinic acid inhibits DOI-induced head shakes in mice
1Pharmacology Research, Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Abstract:
Quinolinic acid, a metabolite of tryptophan in the kynurenine pathway, inhibited the 5-HT(2A/2C) direct agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino propane hydrochloride (DOI) induced head shakes in mice in a dose-dependent manner. This effect was observed 10 min after intracerebroventricular (i.c.v.) administration of 0.0625-1 microg/mouse. 3-Hydroxyanthranilic acid, which is the immediate stable precursor of quinolinic acid in the kynurenine pathway, showed a similar effect 60-120 min after subcutaneous (s.c.) administration, without showing any effect 10 min after i.c.v. administration or 20-40 min after s.c. administration. These observations suggest that quinolinic acid can alter central effects mediated via 5-HT2A receptors.