[Kynurenine protection against ethanol-induced disorders of the burrowing reflex in mice and rats]. / Zashchita kinureninami vyzyvaemykh étanolom narushenii norkovogo refleksa u myshei i krys.

Ethanol (1 g/kg, orally) disturbed the hole reflex in male SHR and C57BL/6 mice and common albino rats increasing the time spent in the light part of a dark-light chamber. In mice this effect was often accompanied by an increase in number of transitions between dark and light compartments. Intraperitoneal pretreatment with endogenous metabolites of tryptophan in the kynurenine pathway of its metabolism (kynurenines)--kynurenic, picolinic and xanthurenic acids--attenuated the effect of ethanol in mice. Injection into the brain ventricles of the most active kynurenines from the group of excitatory amino acids, quinolinic acid and its precursor kynurenine, counteracted ethanol in mice and rats. The same was true in mice for intracerebroventricularly administered kynurenic, picolinic and xanthurenic acids.

[Changes in the burrowing reflex of mice and rats under the influence of kynurenines]. / Izmeneniia norkovogo refleksa myshei i krys pod vliianiem kinureninov.

Behaviour of SHR, C57B1/6 male mice and common albino male rats treated intracerebroventricularly or intraperitoneally with kynurenine, quinolinic, kynurenic, picolinic, xanthurenic, anthranilic acids and nicotinamide, was studied in the dark/light chamber. Quinolinic acid and its precursor kynurenine diminished dark preference, increased the number of transitions between dark and light compartments, diminished locomotion in light compartment. Biogenic amine phenylethylamine with its typical anxiogenic activity, exerted a similar action. Diazepam acted in the opposite way. Noncompetitive antagonist of the NMDA receptors, kynurenic acid, prevented the effect of quinolinic acid. The hole reflex appears to be a useful simple object to study neuroactive endogenous compounds on.

[Plasma kynurenine levels and the dexamethasone test in patients with endogenous anxiety disorders and depression]. / Kinurenin plazmy krovi i deksametazonovyi test u bol'nykh s éndogennoi trevogoi i depressiei.

As many as 30 patients with affective psychoses were examined for the concentration of plasma kynurenine, a neuroactive tryptophan metabolite, and for the parameters of the dexamethasone test. A group of patients suffering from "endogenous anxiety" and endogenous depression were distinguished. In the patients' group with "endogenous anxiety", the concentration of kynurenine at the height psychosis was significantly higher as compared to controls, correlating with the gravity of anxious symptomatology. In the patients' group with endogenous depression, plasma kynurenine was significantly lower than in controls but did not agree with the depression gravity. The dexamethasone test appeared pathological only in the group of patients suffering from endogenous depression and its parameters correlated well with the gravity of depressive symptomatology. In both groups, the study parameters returned to normal after the egress from the morbid condition.

[Species differences in the behavioral effects of cerulein--an agonist of the receptors of the octapeptide cholecystokinin--in white mice and rats]. / Vidovye razlichiia v povedencheskikh éffektakh tseruleina--agonista retseptorov oktapeptida kholetsistokinina--u belykh myshei i krys.

It has been shown in the behavioural experiments that combined pretreatment with haloperidol (0.25 mg/kg) and caerulein (40 micrograms/kg), and to a lesser extent pretreatment with caerulein alone caused long-term reversal of amphetamine (2 mg/kg) induced hyperexcitability in rats. Administration of proglumide (50 mg/kg), an antagonist of CCK-8 receptors, did not reverse long-term antiamphetamine effect of caerulein. In mice pretreatment with caerulein (50 and 100 micrograms/kg) alone or in combination with haloperidol (0.25 mg/kg) caused hypersensitivity to the behavioural effect of amphetamine (3 mg/kg). Intraventricular (I ng), but not systemic (100-500 micrograms/kg) administration of caerulein selectively antagonized seizures in mice induced by intraventricular administration of quinolinic acid (5 micrograms) and N-methyl-D-aspartate (0.2 microgram). Pretreatment with proglumide (50 mg/kg) reversed the anticonvulsive effect of caerulein in mice. In rats, caerulein failed to affect the seizures caused by intraventricular administration of quinolinic acid. The results of the present study demonstrate the existence of obvious interspecies differences in the behavioural effects of caerulein, the agonist of CCK-8 receptors, in mice and rats.

[Changes in dexamethasone test indices and reduction in the rate of serotonin absorption by thrombocytes in chronic alcoholics]. / Izmenenie pokazatelei deksametazonovogo tests i snizhenie skorosti pogloshcheniia serotonina trombotsitami u bol'nykh khronicheskim alkogolizmom.

Seventy-one chronic alcoholics with affective disorders were studied for the dexamethason test (DT) and for the rate of platelet serotonin absorption (RPSA) prior to and following the treatment. A considerable part of the patients displayed pathological changes in DT which correlated with the degree of affective symptomatology. The DT may serve as one of the methods for diagnosing affective disturbances in alcoholism. The RPSA was equally depressed in all the patients studied (by about 30% as against the control group) irrespective of the severity of affective symptomatology. The increase in the activity of central serotoninergic processes expressed in a RPSA decrease seems to reflect an underlying basic biochemical pathology of alcoholism rather than disorders in the affective sphere.

[Stimulatory effects of intraventricular administration of kynurenines, amino acids, and convulsants: differences between rats and mice]. / Vozbuzhdaiushchie éffekty vvedennykh v zheludochki mozga kinureninov, aminokislot i konvul'santov: razlichiia mezhdu krysami i myshami.

Quinolinic acid appeared to be the only kynurenine metabolite among tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitation and clonic seizures in rats whereas all of them exerted convulsant action in mice. Excitatory 1-glutamic and 1-aspartic amino acids and inhibitory amino acids GABA, 1-glycine and taurine did not induce either excitation of seizures in rats but did so in mice. Moreover, GABA, 1-glycine and taurine induced obvious sedation, side position and discoordination in rats. Convulsants strychnine sulfate and pentylenetetrazol induced seizures both in rats and in mice. The differences between mice and rats seem to be due to better availability of hippocampus for the intraventricularly administered drugs in mice. Mice seem to be preferable for studies with intraventricularly administered excitatory amino acids including kynurenines, whereas rats are preferable for inhibitory amino acids.

[Changes in hepatic tryptophan pyrrolase activity and plasma 11-hydroxycorticosteroid levels in rats after single and protracted alcohol administration and withdrawal]. / Izmenenie aktivnosti triptofanpirrolazy pecheni i urovnia 11-oksikortikosteroidov plazma krovi krys pri odnokratnom i dlitel'nom prieme étanola i posle ego otmeny.

Single administration of ethanol in doses of 3 and 5 g/kg per os caused a 4--5fold increase in plasma 11-hydroxycorticosteroids after one hour and an approximately 2 fold increase in liver tryptophan pyrrolase activity after 5 hours. Adrenalectomy abolished the effect of ethanol. Prolonged alcoholization of rats with 2--10% solutions of ethanol ad libitum resulted in the decreased tryptophan pyrrolase activity 2 months after the experiment was initiated. This effect seems likely to be accounted for by the inhibition of the synthesis of this enzyme and its activation by steroid hormones. Withdrawal of ethanol after 2-month alcoholization was associated with an appreciable potentiation of tryptophan pyrrolase activity.

[Different effects of kynurenines on rat liver tryptophan pyrrolase activity]. / Razlichnoe vliianie kinureninov na triptofanpirrolaznuiu aktivnost' pecheni krys.

3-Hydroxyanthranilic, quinolinic and nicotinic acids/50 mg/kg, intraperitoneally/increased the content of rat blood plasma 11-hydroxycorticosteroids as well as the activity of liver tryptophane pyrrolase. After administration of anthranili and picolinic acids, elevation in 11-hydroxycorticosteroid content was not followed by an increase in the tryptophane pyrrolase activity. Picolinic acid diminished induction of tryptophane pyrrolase activity by hydroxycortisone and anthranilic acid dicc not affect the induction. Adrenalectomy prevented the increase in tryptophane pyrrolase activity after treatment with nicotinic, quinolinic and 3-hydroxyanthranilic acids. Prolonged augmentation of kynurenines in the organism might be a result of a mediated through corticosteroids increase in the tryptophane pyrrolase activity caused by elevation in the level of 3-hydroxyanthranilic, quinolinic and nicotinic acids.

[Effect of kynurenine and its metabolites on the concentration of 11-hydroxycorticosteroids in rat plasma]. / Vliianie kinurenina i ego metabolitov na kontsentratsiiu 11-oksikortikosteroidov v plazme krovi krys

Injections of kynurenine (10 and 25 mg/kg, i.p.) and nicotinic acid (50 mg/kg i.p.) produced a marked increase in concentration of 11-hydroxycorticosteroids (11-HCS) in rat blood plasma. Effect of nicotinic acid was not prevented by dexamethazone (0.6 mg/kg). Subtreshold dose of nicotinic acid (10 mg/kg) enhanced a rise in 11-HCS produced by swimming stress. 3-hydroxykynurenine, 3-hydroxyanthranilic, antranilic picolinic and quinolinic acids (10-50 mg/kg) did not change the concentration of 11-HCS. It is suggested that some of the biochemical and pharmacological effects of injected kynurenine can be mediated through the rise of 11-HCS in blood.