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I P Lapin

Publications and source records attributed to I P Lapin.

At least 19 recordsLinked to original sources
PubMed2003

Neurokynurenines (NEKY) as common neurochemical links of stress and anxiety.

The following NEKY have been studied: 1-kynurenine (KYN), 3-hydroxyKYN (3HKYN), kynurenic (KYNA), anthranilic (ANT), 3-hydroxyANT (3HANT), quinolinic (QUIN), picolinic (PICA), xanthurenic (XAN), nicotinic (NIC) acids, 3-indole-pyruvate (IPA), nicotinamide (NAM). NEKY antagonize the central effects of precursors of serotonin (tryptophan and 5-HTP), and tryptamine as well. Seizures induced by central administration of KYN and QUIN are prevented by centrally injected dopamine and diminished by noradrenaline and adrenaline. KYN, 3HANT, PIC and NIC potentiate oxotremorine hypothermia mediated by acetylcholine. Central administration of GABA, glycine or taurine, as well as proline and melatonin, prevented seizures induced by QUIN and KYN. Behavioral inhibitory effects of these amino acids are diminished by pretreament with KYN, 3HKYN and QUIN. Elevation of concentrations of corticosteroids is resulted in rise of level of NEKY due to hormonal induction of liver tryptophan pyrrolase and brain 2,3 dioxigenase. NEKY, in their turn, activate both enzymes. Thus, a "vicious circle" is formed and it supports an elevated level of NEKY for a long time, hours and days. Long-lasting increased concentrations of NEKY in tissues can lead to significant after-effects and numerous pathogenic consequences. One can not exclude that a rise of the level of some NEKY, e.g. KYNA, IPA, PIC and XAN, may play an "adaptogenic" role in stress antagonizing some pathologic effects of KYN and QUIN, e.g. anxiogenic, neurotoxic and proconvulsive. It has been demonstrated that the excitatory NEKY, KYN, 3HKYN, QUIN, possess an anxiogenic activity in the standard animal models of anxiety. NEKY with opposite neuroactivities, namely KYNA, IPA, PICA and XAN, have a pharmacological profile of anxiolytics and antagonize both anxiogenic NEKY and standard anxiogens, like caffeine, pentylenetetrazole and yohimbine. Major emphasis is made on KYN as a putative endogenous anxiogen. Studies on the interaction of NEKY with other endogenous metabolites involved in anxiety (beta-phenylethylamine, cholecystokynine, melatonin) are in progress.

Animals↗
PubMed1998

Antagonism of kynurenic acid to anxiogens in mice.

In a dark-light chamber in mice, kynurenic acid (KYNA, 200 mg/kg, i.p.), an endogenous neuroactive metabolite of tryptophan, attenuated the most stable effect of anxiogens in this model of anxiety--a decrease in the rate of leanings-out of the dark compartment --induced by caffeine, pentylenetetrazole and yohimbine, but not by beta-phenylethylamine (PEA). KYNA by itself did not alter behavior of mice in the chamber, in contrast to what has been observed in an elevated plus-maze, another model of anxiety, where KYNA had an anxiolytic pharmacological profile.

Animals↗
PubMed1998

Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenetetrazole in mice.

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.

Animals↗
PubMed1997

Modulation of the inhibitory effect of phenylethylamine on spontaneous motor activity in mice by CPP-(+/-)-3-(2-carboxypiperazin-4-YL)-propyl-1-phosphonic acid.

Beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous, motor activity in mice. CPP- (+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antagonizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pretreament with noncompetitive antagonists of NMDA receptors, such as dizocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperidol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagonize the inhibitory effect of other tested drugs such as diazepam, haloperidol, baclofen and phenibut. Intracerebroventricularly administered NMDA (0.2 microM), an agonist of NMDA receptors, suppressed the antagonistic effects of CPP against PEA. This suggests that anti-PEA effect of CPP is related to NMDA receptors. Anti-PEA effect of CPP is not due to accelerated deamination of PEA in CPP-treated mice. When small doses of PEA (5 and 10 mg/kg) and CPP (0.2 and 1 mg/kg) were used, the synergism of two drugs was observed. CPP (1 mg/kg) and deprenyl (0.5 mg/kg) an inhibitor monoamine oxidase of B type (MAO-B), had additive effects on PEA-induced inhibition of locomotion. This effect was not associated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 microM) or low (4.3 microM) concentration of PEA as a substrate in the medium. Mechanism of the interaction of CPP and PEA, two drugs belonging to different groups of biologically active compounds, deserves further studies.

Animals↗
PubMed1996

Antagonism by CPP (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, of beta-phenylethylamine (PEA)-induced hypermotility in mice of different strains.

In male C57BL/6, BALB/c, and SHR (bred from Swiss) mice, pretreatment with (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive antagonist of N-methyl-D-aspartate (NMDA) receptor, attenuated the hyperlocomotion induced by beta-phenylethylamine (PEA). This effect of CPP was blocked by intracerebroventricularly (ICV) administered NMDA (0.2 nM). CPP did not alter the hyperlocomotion induced by d-amphetamine. PEA rarely inhibited spontaneous motor activity in those strains. Two other competitive antagonists of NMDA, 2-amino-5-phosphonopentanoic acid (AP-5) and 2-amino-7-phosphonoheptanoic acid (AP-7), ICV at doses of 0.01-0.1 microgram, were ineffective. The noncompetitive antagonists of NMDA, dizocilpine (MK-801) and phencyclidine, at subthreshold doses of 0.1-0.5 mg/kg, potentiated the stimulant effect of PEA. In earlier studies we also observed antagonism between CPP and PEA in NIH-Swiss mice, a strain in which PEA inhibits locomotion. Relationships between the stimulant and the anxiogenic effects of PEA are discussed.

Animals↗
PubMed1995

Effects of D1 and D2 dopamine receptor antagonists and catecholamine depleting agents on the locomotor stimulation induced by dizocilpine in mice.

Low doses of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) induce locomotor stimulation in mice, whereas higher doses are associated with ataxia, stereotyped behaviors and catalepsy. We investigated the role of dopamine receptors and presynaptic dopamine neurons in the locomotor effects of dizocilpine. For comparison, we studied several other drugs that induce locomotor stimulation in mice. Pretreatment of male mice with haloperidol (0.1 mg/kg, i.p.) completely prevented the stimulation of normally coordinated locomotion induced by a non-intoxicating dose of dizocilpine (0.1 mg/kg, i.p.); haloperidol also attenuated the locomotor stimulation produced by phencyclidine (PCP, 1 and 2 mg/kg, i.p.), d-amphetamine (2 and 5 mg/kg, i.p.) and diazepam (0.5 mg/kg, i.p.). Haloperidol (doses up to 2.5 mg/kg) did not attenuate the ataxia and decreased locomotion induced by higher doses of dizocilpine (1 and 2 mg/kg). The active cis isomer of flupenthixol (0.5 mg/kg, i.p.), an antagonist of both D1 and D2 dopamine receptors, also diminished the stimulant actions of all of the test drugs, whereas its inactive trans form did not. The selective D1 antagonist R(+/-)-SCH 23390 (0.1 mg/kg) and the selective D2 antagonist raclopride (1 mg/kg) had little effect on the stimulatory effect of dizocilpine, although they did reduce the stimulation produced by PCP, d-amphetamine and diazepam. However, pretreatment with a combination of R(+/-)SCH 23390 and raclopride completely prevented dizocilpine-induced locomotor stimulation. Pretreatment with alpha-methyl-p-tyrosine (AMPT, 50 and 250 mg/kg), an inhibitor of tyrosine hydroxylase, or with 6-hydroxydopamine (6-OH-DA, 50 micrograms, i.c.v.), a neurotoxin that destroys brain dopaminergic and noradrenergic neurons, did not attenuate the locomotor stimulation induced by dizocilpine, although these treatments did reduce the stimulant effects of d-amphetamine. In AMPT or 6-OH-DA pretreated mice, haloperidol (0.125 mg/kg) prevented the stimulatory effect of dizocilpine. These results support a role for dopamine receptors in the stimulation of normally coordinated locomotion by dizocilpine. However, the locomotor stimulant effect of dizocilpine, unlike that of d-amphetamine, can be expressed in the presence of D1 or D2 dopamine receptor blockade and does not appear to be dependent on intact presynaptic mechanisms.

Animals↗
PubMed1995

Only controls: effect of handling, sham injection, and intraperitoneal injection of saline on behavior of mice in an elevated plus-maze.

In male NIH-Swiss mice intraperitoneal injection of physiological saline significantly diminished (vs. naive mice) the ratio of the number of entries into open arms over the sum of entries into open and closed arms, and significantly prolonged time spent in closed arms. These two effects are considered to be typical for anxiety-inducing drugs (anxiogens). The time spent in open arms and at the intersection was unaffected. An equal number of entries into closed and also open arms was observed among fast- and slow-moving individuals. This is an argument against using the number of entries into arms as a measure of locomotor activity of mice. Additional measurement of locomotor activity in actometers is needed to check whether drugs used in experiments with elevated plus-maze alter locomotor activity. Injection of saline significantly shortened the latency of reaching one of the closed arms from the free end of an open arm. Handling, sham injection, and injection significantly diminished the shortening of latency in a second experiment (vs the latency in the first one), a parameter used as a criterion of memory and learning. Thus, saline-treated groups taken as controls in pharmacological experiments possess the behavioral profile of stressed and anxious animals in an elevated plus-maze, a device used as a model of anxiety and a model for studying memory and learning in mice and rats.

Analysis of Variance↗
PubMed1994

[Linear, circadian and age-related differences in the burrowing reflex in mice and its alteration by ethanol].

The hole reflex (darkness preference) was stable in the C57BL/6 and CC57BR strains by day and in the evening, whereas its was only stable in the evening in the SHR. Intensity of locomotion was the highest in the evening in the C57BL/6 strain. The transition rate between dark and light chambers was the same by day and in the evening in all the strains. The C57BL/6 mice were much more resistant against ethanol-induced alterations of the hole reflex than the SHR.

Aging↗
PubMed1994

Antiethanol effects of indol-3-ylpyruvic acid in mice.

Indol-3-ylpyruvic acid (IPA, 10-100 mg/kg), an endogenous metabolite of tryptophan, shortened ethanol anaesthesia in C57Bl/6 male mice and diminished the post-ethanol (23 hr) inhibition of locomotion. In an elevated plus-maze, IPA had an anxiolytic effect in short-sleep, but not in long-sleep, mice. IPA did not modify ethanol-induced or caffeine-induced stimulation of spontaneous locomotion or the anxiogenic effect of pentylenetetrazole in an elevated plus-maze. The probable involvement of IPA in the defence mechanisms in alcoholism is suggested.

Alcohol Drinking↗
PubMed1994

[The use of baclofen for treating affective disorders in alcoholism].

90 patients with alcoholism stage II suffering from secondary affective disorders (anxiety, depression) were divided into 4 groups: treated with GABA-B-receptor ligand baclofen (group 1), with sibazon (group 2), amitriptylin (group 3), placebo (group 4). As shown by clinical, experimental psychological and electrophysiological examinations, baclofen is not inferior in efficacy to sibazon and amitriptylin, but is free of side effects and complications typical for the above drugs (central deprivation, addiction, etc.). MAO activity was unaffected in all the patients, so were dopamine, serotonin and GABA blood concentrations after the treatment. This does not allow to relate the peripheral metabolism of GABA and monoamines to emergence of secondary affective disorders in alcoholism. The authors think promising to seek for drugs effective against affective disorders among ligands of GABA-B receptors.

Adult↗
PubMed1993

Anxiolytic effect of indole-3-pyruvic acid (IPA) in mice.

In an elevated plus-maze indole-3-pyruvic acid (IPA, 100-200 mg/kg), an endogenous metabolite of tryptophan, possesses in mice an activity typical of anxiolytics. IPA increased the ratio of the number of entries into open arms over the total number of entries into open and closed arms and the time spent in open arms. Similar effect was observed for diazepam, a standard anxiolytic. Pretreatment with IPA attenuated the anxiogenic effect of caffeine (50 mg/kg) and 3-hydroxykynurenine (1.2 micrograms, i.c.v.) but not that of pentylenetetrazole (10 mg/kg), or phenylethylamine (5 and 10 mg/kg). Pretreatment with IPA (50-200 mg/kg) did not attenuate pentylenetetrazole- or phenylethylamine-induced seizures in contrast to diazepam which prevents both types of seizures. The data suggest that IPA is an endogenous anxiolytic with novel profile.

Animals↗
PubMed1993

Anxiogenic effect of phenylethylamine and amphetamine in the elevated plus-maze in mice and its attenuation by ethanol.

In previous experiments beta-phenylethylamine (PEA), like the standard anxiogens caffeine, pentylenetetrazole, and yohimbine, has exhibited an anxiogenic effect in the two animal models of anxiety: the social interaction test and the conflict situation test. In the present study, PEA acts as an anxiogen in an elevated plus-maze, diminishing (compared to controls) the ratio of entries into open arms over the total number of entries and shortening the time spent in the open arms. DL-Amphetamine sulfate (AMPH) also had a similar action. These data support the previous suggestion that PEA may belong to the group of endogenous anxiety-inducing compounds. Pretreatment with ethanol prevented the effects of both PEA and AMPH.

Amphetamine↗