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N K Popova

Publications and source records attributed to N K Popova.

At least 19 recordsLinked to original sources

Effect of imipramine on the behavior and cerebral 5-HT1A serotonin receptors in mice genetically predisposed to catalepsy.

Acute injection of imipramine to NPK mice hereditary predisposed to pinching catalepsy reduced immobility in the forced swimming test, but had no effect on catalepsy. Chronic treatment with imipramine reduced the severity of catalepsy and functional activity of 5-HT1A serotonin receptors, but did not modify their expression in the hippocampus. NPK mice can be a convenient model for studies of the effects of antidepressant.

Adrenergic Uptake Inhibitors↗

Acquisition and extinction of a conditioned passive avoidance reflex in mice with genetic knockout of monoamine oxidase A.

We report here the results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in mice with genetic knockout of monoamine oxidase A (MAO A) and the progenitor line C3H. Mice of both lines acquired the conditioned passive avoidance reaction efficiently. Mice with genetic knockout of MAO A were characterized by prolonged retention of reproduction of the memory trace, as compared with rapid extinction in C3H mice. Smaller numbers of transfers, and vertical rearings on days 7-13 and the numbers of glances into and rom the dark sector on days 11-13 of extinction in MAO A-knockout mice appear to reflect their more marked fear reactions when confronted with the "dangerous" sector, along with increased anxiety, these facilitating longer-lasting retention of the memory trace.

Analysis of Variance↗

[The stress effect in the prenatal period on sexual excitation and sexual orientation of the mice males].

Estrus female behind holed transparent partition produced sexual motivation and sexual arousal in males. It was manifested in behavioral changes (an increase in time spent near the partition) and the testosterone level augmentation in blood. Female mice were exposed to stress (1 h/day restraint) in the last week of gestation. Prenatal stress was shown to decrease the blood corticosterone level as well as to diminish sexual motivation and sexual arousal in adult male mice. Estrus female exposure produced a lesser behavioral response and a lesser testosterone level augmentation. No changes in weight of testicles, seminal vesicles or adrenal glands were found, but preputial gland weight increased. In prenatally stressed males, a female preference decrease and a male preference increase were revealed in the partner preference test. These data suggest that prenatal stress decreases sexual motivation in males and leads to clear predisposition to homosexuality, although it does not produce complete inversion of sexual orientation.

Adrenal Glands↗

[Effect of long-term cold adaptation on the mRNA expression of serotonin 5-HT1A and 5-HT2A receptors].

The mRNA expression of serotonin receptors 5-HT1A and 5-HT2A was investigated by the quantitative method RT-PCR in rats adapted to cold (5 weeks at +4 -(+6) degrees C) and in control (5 weeks at +20-22 degrees C). Four brain regions were examined: frontal cortex, hypothalamus, hippocampus, and midbrain. The influence of cold adaptation on the mRNA expression of 5-HT15 receptor was not found to be absent. The mRNA expression of 5-HT2A receptor changed under long-term cold exposure. These changes in different brain regions were various: in hypothalamus, there was an increase of the 5-HT2A receptor mRNA expression; in the cortex, a decrease; in the hippocampus and midbrain, significant changes of the mRNA expression were absent. The findings appear bo te adaptive and, according to their localization in the central nervous system, regulatory. They also suggest involvement of brain serotoninergic system in mechanism of adaptive reorganization of temperature regulation.

Acclimatization↗

Effects of experimental increases and decreases in thyroxine levels on the extent of cataleptic freezing reactions in rats.

Numerous clinical observations have provided evidence for a tight connection between impairments in the functions of the hypothalamo-hypophyseal-thyroid system and nervous and mental disorders. The aim of the present work was to compare the effects of experimental decreases and increases in blood thyroxine levels on the extents of two types of pathological freezing reaction in male Wistar rats--spontaneous catalepsy and catalepsy evoked by pinches at the nape of the neck (pinch-induced catalepsy). Chronic administration of the thyroxine synthesis inhibitor propylthiouracil (5 mg/kg/day for 28 days) significantly decreased the blood hormone level and sharply increased the proportion of animals showing spontaneous catalepsy and the immobility time, but had no effect on the extent of pinch-induced catalepsy. At the same time, chronic administration of thyroxine (0.1 mg/kg/day for 28 days), which produced significant increases in blood hormone levels, had no effect on the extent of spontaneous catalepsy but significantly increased the proportion of animals showing pinch-induced catalepsy and the duration of this type of catalepsy. It is concluded that both insufficiency and excess of thyroid hormones have cataleptogenic actions, but enhance different types of catalepsy.

Animals↗

Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains.

The brain neurotransmitter serotonin is involved in the regulation of aggressive behavior. The main factor determining the brain serotonin level is the activity of the rate-limiting enzyme in the biosynthesis of the neurotransmitter--tryptophan hydroxylase isoform (TPH) 2 encoded by the Tph2 gene. Recently the C1473G single-nucleotide polymorphism in the Tph2 gene was reported. Here we study the C1473G polymorphism in 10 inbred mouse strains (C57BL/6J, AKR/J, DD/He, C3H/HeJ, YT/Y, BALB/cJLac, CC57BR/Mv and A/He) and demonstrate the association of the polymorphism with brain TPH activity and intermale aggressiveness. TPH activity in the midbrain of mice homozygous for the 1473C allele was higher than that in mice carrying 1473G alleles. A close association of the 1473C allele with increased number of attacks towards another male was found. The results support a link between the C1473G polymorphism in Tph2 gene, tryptophan hydroxylase activity and intensity of intermale aggression.

Aggression↗

[Selection for the predisposition to catalepsy enhances depressive-like traits in mice].

Immobility reaction or catalepsy is a natural passive defensive (lurking) behavioral response to the appearance of a predator. Selection for high predisposition to catalepsy has been performed in a population of (CBA x (CBA x AKR)) backcrosses of the crossing between mouse lines sensitive and resistant to catalepsy (VBA and AKR, respectively). A rapid increase in the number of animals with catalepsy has been observed: from 23% in backcrosses to 71% in the S3 generation. Selection for catalepsy does not affect mouse anxiety in the open field and plus-maze tests. However, S8 and S9 mice are characterized by a decreased motor activity in the open-field test and an increased immobility in the forced swim and tail suspension tests, which is interpreted as an increase in "depressiveness." The results indicate that genetically determined catalepsy is related to depressive-like characteristics of defensive behavior.

Animals↗

Effect of monoamine oxidase gene knockout on dopamine metabolism in mouse brain structures.

Experiments were performed on knockout Tg8 mice lacking monoamine oxidase A gene that plays a major role in dopamine catabolism. The study by the method of high-performance liquid chromatography revealed considerable regional differences in the contents of dopamine and its metabolite dihydroxyphenylacetic acid in brain structures of these animals. Tg8 mice differed from the parent C3H/HeJ strain by low level of dihydroxyphenylacetic acid in the striatum, midbrain, hypothalamus, and hippocampus and high concentration of dopamine in the striatum. No differences were revealed in the contents of dopamine and dihydroxyphenylacetic acid in the frontal cortex and amygdala. The 2.4-4.8-fold decrease in the content of dihydroxyphenylacetic acid in various brain structures was not accompanied by changes in dopamine concentration. These data reflect the effective compensation for deficiency of dopamine metabolism. Our results suggest that monoamine oxidases A and B and catechol-O-methyltransferase play different roles in dopamine metabolism in various brain structures.

3,4-Dihydroxyphenylacetic Acid↗

Correlation between cataleptic freezing and prepulse inhibition of the startle reflex in rats.

GC rats, bred for a predisposition to cataleptic freezing, were found to show a significant negative correlation between the duration of freezing and the level of prepulse inhibition of the startle reflex. In addition, a group of GC rats characterized by increased "nervousness" also showed a negative correlation between the duration of freezing and the extent of habituation of the startle reflex. These correlations were not seen in Wistar rats. Since decreases in the level of prepulse inhibition and habituation of the startle reflex are regarded as characteristic of schizophrenia, it is suggested that cataleptic freezing in GC rats might be used as a model of schizophrenic pyschopathology.

Acoustic Stimulation↗

The roles of different types of serotonin receptors in activation of the hypophyseal-testicular complex induced in mice by the presence of a female.

Placing of receptive females in the sector of a cage separated by a partition preventing physical contact but allowing sight and olfaction induced increases in blood testosterone levels in male mice. The selective agonist of 5-HT1A receptors 8-OH-DPAT (0.1 mg/kg) and the mixed 5-HT1A/1B receptor agonist eltoprazine (3.0 and 10.0 mg/kg) blocked the activatory effect of presentation of females on the hypothalamohypophyseal-testicular complex (HHTC) in males, while the 5-HT1A receptor antagonist p-MPPI (0.2 mg/kg) prevented the inhibitory effects of 8-OH-DPAT and eltoprazine. The 5-HT1B receptor agonist CGS-12066A (1.0 and 2.0 mg/kg) had no effect, while the mixed 5-HT1B/2C agonist TFMPP (5.0 mg/kg) blocked the increase in blood testosterone in males in response to presentation of females. The 5-HT2A receptor antagonist ketanserin (1.0 and 2.0 mg/kg) prevented the increase in testosterone induced by the presence of females. The 5-HT3 receptor antagonist ondansetron (0.05 and 0.1 mg/kg) increased the initial plasma testosterone level but blocked activation of the HHTC induced by the presence of receptive females. These results led to the conclusion that 5-HT receptors are involved in controlling the sexual activation of males. Different types and even subtypes of the same type of 5-HT receptor had different effects, both inhibitory and activatory, on activation of the HHTC by receptive females. Blockade of HHTC activation induced by the presence of females appears to involve 5-HT1A and 5-HT2C receptors, while activation involves 5-HT2A and 5-HT3 receptors.

Animals↗

[Effect of experimental elevation and decrease of thyroxine level on catalepsy in rats].

Thyroid dysfunction is associated with mental disorders. The present study was aimed to reveal the effects of experimental decrease and increase of thyroxine level on expression of two types of extensive freezing: spontaneous and pinch-induced catalepsy, in Wistar rat males. Chronic administration of thyroxine synthesis inhibitor, propylthiouracil (5 mg/kg/day, 28 days), markedly decreased plasma hormone level and at the same time produced a significant increase in percentage of spontaneously cataleptic animals and immobility time, but had no effect on the expression of pinch-induced catalepsy. On the contrary, chronic thyroxin (0.1 mg/kg/day, 28 days) treatment produced no effect on spontaneous catalepsy expression, although it significantly increased percentage of cataleptic animals and immobility time of pinch-induced catalepsy. The results suggest that both the thyroid hormone deficit and excess provoke catalepsy in rats but enhance different forms of freezing reaction.

Animals↗

[The role of brain serotonin in the expression of genetically determined defensive behavior].

The review summarizes the results of long-term studies on the role of the brain mediator serotonin and genetic predisposition to various types of defensive behavior. The involvement of the serotonergic brain system in the mechanisms of genetic control of both active and passive defensive responses has been established using silver foxes, Norway rats of S40 selection for low and high aggressiveness to humans, aggressive mice with genetic knockout of monoaminoxidase A, and S40 rats selected for predisposition to passive defensive response of freezing (catalepsy). The changes in the serotonergic 5-HT1A-brain receptors of rats genetically predisposed to different strategies of defensive behavior were similar. However, the activity of the key enzyme of serotonin biosynthesis and the brain structures, in which serotonin metabolism was altered, significantly differed with regard to the preferred strategy. The conclusion was drawn that the 5-HT1A-receptors and enzymes of serotonin metabolism in the brain are involved in implementing genetic control of defensive behavior. Expression of the 5-HT1A-brain receptors was suggested to determine the levels of fear and anxiety and, consequently, the predisposition to defensive behavior, whereas the preferred strategy of defensive response (active or passive defensive) depends on genetically determined features of serotonin metabolism in the brain structures.

Animals↗

[Polymorphism of the serotonin system genes in some Finno-Ugric populations].

Polymorphic sites in the genes encoding monoamine oxidase A (MAO-A), serotonin transporter (hSERT) and 5-HT2A receptor were typed in Khant and Komi ethnic groups with the purpose of revealing possible interpopulation differences in genotype and allele frequencies. No statistically significant differences in the hSERT and 5-HT2A gene frequencies were detected. At the same time, the populations examined had statistically significantly different MAO-A genotype and allele frequencies. These results obtained indicate the prevalence of the site gain alleles of the EcoRV and Fnu4HI RFLP loci at the MAO-A gene in Komis and the of the corresponding site loss alleles in Khants.

Alleles↗

Hypothalamic tryptophan hydroxylase and the hypothalamic-pituitary-adrenocortical response to water deprivation and hydration in vasopressin-deficient and normal rats.

The effects of water deprivation and hydration on plasma corticosterone concentration and the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, in the hypothalamus of vasopressin- (AVP-) deficient homozygous Brattleboro and normal Wistar rats were studied. In the Wistar rats, water deprivation caused an increase in the TPH activity in the anterior and middle (infundibular) parts of the hypothalamus, while hydration did not affect the activity of the enzyme in the anterior hypothalamus but produced an increase in its middle part. In contrast, in the Brattleboro rats, water deprivation had no effect on TPH activity in the anterior and middle parts of the hypothalamus but hydration produced a decrease in TPH activity in the anterior hypothalamus. After 48 h of water deprivation, the plasma corticosterone concentration significantly increased in water-deprived and decreased in hydrated Wistar rats. Under water deprivation, the rise in corticosterone concentration in the homozygous Brattleboro rats was significantly greater than that in the Wistar rats. The data provide evidence that the CRH-like activity of AVP is not necessary for activation of the hypothalamic-pituitary-adrenal system induced by water deprivation. The observations show that AVP is involved in the activation of TPH induced by water deprivation. This suggests that AVP modulates the metabolism of 5-HT and the response of the 5-HT-ergic system to water deprivation.

Animals↗

Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual arousal in male mice.

The presence of a sexually receptive female behind a partition that prevents physical contact, but not seeing or smelling, increases blood testosterone level and induces the specific behavior in CBA male mice so that they more frequently approach the partition and spend more time near it in an attempt to make their way to the female. Treatment with the selective 5-HT(1A) serotonin receptor agonist 8-OH-DPAT (0.1, 0.25, 0.5 and 2.0 mg/kg) induced a dose-dependent decrease in the amount of time spent by the males near the partition, or "partition time", which is considered the main pattern of sexual motivation. The activating effect of female exposure on the male's pituitary-testicular system was totally blocked, as no increase in plasma testosterone level was observed. The 5-HT(1A) antagonist p-MPPI (0.1, 0.2 and 0.4 mg/kg) itself did not affect behavior or alter plasma testosterone, but attenuated the inhibiting effect of 8-OH-DPAT on behavior and totally antagonised the effect of the 5-HT(1A) agonist on testosterone response. The 5-HT(1B) agonist CGS-12066A (1.0 and 2.0 mg/kg) has no influence on the plasma testosterone increase exhibited by the male in response to female exposure. At the same time, either dose of CGS-12066A significantly reduced the partition time. The conclusion was made that the 5-HT(1A) subtype is involved in controlling both behavioral and hormonal indices of sexual arousal in male mice, while the 5-HT(1B) receptors antagonise sexual motivation, but do not modify the hypothalamic-pituitary-testicular response.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effect of monoamine oxidase A knockout on resistance to long-term exposure to ethanol.

It was shown that transgenic Tg8 mice with monoamine oxidase A (MAO A) gene knockout demonstrate higher resistance to acute ethanol exposure compared to wild type C3H mice. This difference was observed at the early age (28-30 days). Long-term ethanol treatment changed the resistance to hypnotic, but not hypothermic action of this agent. Seven-day exposure increased the resistance to ethanol-induced narcotic sleep in Tg8 and C3H mice. After 30-day ethanol treatment the duration of narcotic sleep sharply decreased in C3H mice and increased in Tg8 mice, which attested to their decreased tolerance to ethanol.

Aging↗

Effect of chronic administration of imipramine on 2A-serotonin receptor mRNA in brain cortex of rats predisposed and resistant to catalepsy.

Rats selected by predisposition to catalepsy showed decreased level of 2A-serotonin receptor mRNA in the frontal cortex in comparison with Wistar rats (p<0.05). Chronic administration of tricyclic antidepressant imipramine hydrochloride 2-fold increased the content of receptor mRNA in genetically cataleptic rats (p<0.001) and did not change this parameter in Wistar rats. These results prompted us to revise current notion on the mechanisms of chronic effect of imipramine on 2A-serotonin receptors.

Animals↗