ABSTRACT
Melatonin was tested in an ongoing attempt to find the endogenous antagonists of quinolinic acid, an endogenous convulsant. Among a great number of metabolites that have been tried before, only a few were found (cerulein and quinaldic acid in mice and kynurenic acid in rats). In SHR (bred from Swiss) male mice, intracerebroventricular (i.c.v.) pretreatment with melatonin (1.25-10.0 microg) attenuated (in the descending order of potency) the convulsant effect of i.c.v. administered kainate, quinolinate, glutamate, N-methyl-D-aspartate, and pentylenetetrazole. Melatonin was ineffective against i.p. administered pentylenetetrazole. Systemically (intraperitoneal, i.p.) administered melatonin (12.5-100.0 mg/kg) attenuated the convulsant effect of quinolinate, while the action of other convulsants used remained unaltered. It is suggested that melatonin could be tried against grand mal seizures in epileptic patients.
Subject(s)
Anticonvulsants/pharmacology , Convulsants/antagonists & inhibitors , Melatonin/pharmacology , Seizures/prevention & control , Animals , Brain/drug effects , Convulsants/toxicity , Excitatory Amino Acid Agonists/toxicity , Excitatory Amino Acid Antagonists , Glutamates/toxicity , Injections, Intraperitoneal , Injections, Intraventricular , Kainic Acid/antagonists & inhibitors , Kainic Acid/toxicity , Male , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , N-Methylaspartate/antagonists & inhibitors , N-Methylaspartate/toxicity , Pentylenetetrazole/antagonists & inhibitors , Pentylenetetrazole/toxicity , Quinolinic Acid/antagonists & inhibitors , Quinolinic Acid/toxicity , Seizures/chemically inducedABSTRACT
Quinolinic acid, a metabolite of tryptophan on the kynurenine pathway, shortened the duration of social contacts (sniffings) in C57BL/6 mice which had been previously isolated for 24 h. This effect was observed at the following time intervals after i.c.v. administration: 2-6, 22-26 and 32-36 min. Locomotion was significantly less inhibited and only during the first interval. L-Kynurenine sulphate was less active. It shortened the duration of contacts only during the 32-36 min interval after i.c.v. administration. Grooming was significantly reduced by quinolinic acid at 7-11, 12-16 and 17-21 min after administration. These effects of quinolinic acid in the social interaction test are similar to those of standard anxiogens and suggest that quinolinic acid belongs to the putative endogenous anxiogens (and not only to the endogenous convulsants). The same assumption about L-kynurenine based on data in other models of anxiety has been made previously.
ABSTRACT
The relationship between plasma kynurenine (KYN) concentration and anxiety and depression in psychiatric patients was examined. KYN has been reported as a probable endogenous anxiogen in animal models of anxiety. Thirty patients with affective states were studied. The Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Dexamethazone Suppression Test (DST) and Diazepam Test (DT) were used to differentiate two groups with prevalence of anxious or depressive symptomatology. It was found that in endogenous anxiety, the plasma KYN concentration is increased and in endogenous depression, it is decreased (resp., 1.94 micrograms/ml and 0.62 microgram/ml, versus normal 0.9 +/- 0.07 microgram/ml). After treatment this concentration became normal in both groups. In this study KYN concentration correlated significantly with the severity of anxiety. The results suggest that the increase of plasma KYN concentration in anxiety may be used as an additional criterion to differentiate endogenous anxiety with depressive mood from endogenous depression in clinical practice. DT and DST have also appeared to be reliable factors in differentiation of anxiety and depression.
Subject(s)
Anxiety Disorders/diagnosis , Bipolar Disorder/diagnosis , Depressive Disorder/diagnosis , Dexamethasone , Kynurenine/blood , Adrenal Cortex Hormones/blood , Adult , Anxiety Disorders/blood , Anxiety Disorders/psychology , Bipolar Disorder/blood , Bipolar Disorder/psychology , Depressive Disorder/blood , Depressive Disorder/psychology , Diagnosis, Differential , Double-Blind Method , Female , Humans , Male , Middle Aged , Personality InventoryABSTRACT
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.