Effect of catecholaminergic drugs on quinolinate- and kynurenine-induced seizures in mice.

J Neural Transm Gen Sect

Laboratory of Psychopharmacology, Bekhterev Psychoneurological Research Institute, Leningrad, USSR.

Published: November 1990

Administration of reserpine, trifluperidol, chlorpromazine, haloperidol, spiroperidol, and thioproperazine to adult mice shortened the latency and increased the number of animals with clonic seizures induced by 1-kynurenine sulfate or its metabolite quinolinic acid. Haloperidol dose-dependently intensified kynurenine-induced seizures and did not alter pentylenetetrazole seizures. Dopamine abolished the effect of haloperidol while serotonin was ineffective. Pretreatment with 6-hydroxydopamine potentiated kynurenine-induced seizures, but not quinolinic acid-induced seizures. The seizure thresholds of kynurenine and quinolinic acid were not affected by pretreatments with yohimbine, clonidine, piperoxan, phentolamine and tricyclic antidepressants. Apomorphine and amphetamine (i.p.), noradrenaline and adrenaline (i.c.v.) possess anticonvulsant action against kynurenine and not against quinolinic acid. The data obtained suggest a similarity of kynurenine and known convulsants in the involvement of the catecholaminergic processes in their convulsant action. Quinolinic acid markedly differs from kynurenine in its mechanism of action as indicated by their interactions with numerous endogenous substances.

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF01244834DOI Listing

Publication Analysis

Top Keywords

quinolinic acid
16
kynurenine-induced seizures
12
kynurenine quinolinic
8
seizures
6
quinolinic
5
catecholaminergic drugs
4
drugs quinolinate-
4
quinolinate- kynurenine-induced
4
seizures mice
4
mice administration
4

Similar Publications

Alterations in the kynurenine pathway, and in particular the balance of neuroprotective and neurotoxic metabolites, have been implicated in the pathophysiology of Major Depressive Disorder (MDD) and antidepressant treatment response. In this study, we examined the relationship between changes in kynurenine pathway activity (Kynurenine/Tryptophan ratio), focusing on the balance of neuroprotective-to neurotoxic metabolites (Kynurenic Acid/Quinolinic Acid and Kynurenic Acid/3-Hydroxykynurenine ratios), and response to 8 weeks of selective serotonin reuptake inhibitor (SSRI) treatment, including early changes four weeks after SSRI initiation. Additionally, we examined relationships between kynurenine metabolite ratios and three promising biomarkers of depression and antidepressant response: amygdala/hippocampal volume, and glutamate metabolites in the anterior cingulate cortex.

View Article and Find Full Text PDF

Rat models of postintracerebral hemorrhage pneumonia induced by nasal inoculation with or intratracheal inoculation with LPS.

Front Immunol

January 2025

State Key Laboratory of Traditional Chinese Medicine Syndrome, Department of Neurology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: A stable and reproducible experimental bacterial pneumonia model postintracerebral hemorrhage (ICH) is necessary to help investigating the pathogenesis and novel treatments of Stroke-associated pneumonia (SAP).

Aim: To establish a Gram-negative bacterial pneumonia-complicating ICH rat model and an acute lung injury (ALI)-complicating ICH rat model.

Methods: We established two standardized models of post-ICH pneumonia by nasal inoculation with () or intratracheal inoculation with lipopolysaccharide (LPS).

View Article and Find Full Text PDF

Thrombin-induced kynurenine 3-monooxygenase causes variations in the kynurenine pathway, leading to neurological deficits in a murine intracerebral hemorrhage model.

J Pharmacol Sci

February 2025

Department of Physical Chemistry for Bioactive Molecules, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.

The purpose of the present study is to investigate changes in the kynurenine pathway after intracerebral hemorrhage (ICH) and its effects on ICH-induced injury. The exposure of a primary rat microglial culture to thrombin increased the mRNA level of kynurenine 3-monooxygenase (KMO), and this increase was attenuated by a p38 MAPK inhibitor. Thrombin also increased the protein level of KMO.

View Article and Find Full Text PDF

Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia.

Sci Rep

January 2025

Affiliated Mental Health Centre & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, China.

The tryptophan (TRP)-kynurenine (KYN) pathway is involved in the pathogenesis of schizophrenia. This study aimed to investigate the levels of TRP-KYN metabolites in serum and urine of patients with first-episode schizophrenia (FES) and their association with clinical manifestations. This study included 38 drug-naive patients with FES and 43 healthy controls (HCs).

View Article and Find Full Text PDF

Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!