-
[show abstract]
[hide abstract]
ABSTRACT: ACTH1-24(1 mg/kg) administered to 5-7-day-old rats reduced their locomotor activity and did not alter blood levels of corticosterone. ACTH administration on postnatal days 12-14 increased corticosterone levels, but had no effect on locomotor activity. Thus, the behavioral effect of ACTH is not due to corticotropic action of the hormone and is not associated with blood levels of glucocorticoids.
Bulletin of Experimental Biology and Medicine 01/2013; 154(4):464-6. · 0.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effects of antagonist of α2-adrenoceptors yohimbine and their agonist clonidine on Bax and Bcl-X
L
mRNA levels in neonatal rat brain were studied. Yohimbine decreased Bax mRNA level in the cerebellum, increased the ratio between Bcl-X
L
and Bax mRNA levels in the cerebellum, cortex, and hippocampus, and increased Bcl-X
L
mRNA level in the cortex and hippocampus of 6-day-old-rat pups 24 h after injection. Administration of clonidine 20 min after
yohimbine administration abolished its effect on Bcl-XL mRNA level in the hippocampus. The data obtained indicate that the blockade of α2-adrenoceptors induces antiapoptotic changes in the developing rat brain, some of which can be abolished after coadministration
with the agonist of these receptors.
Biology Bulletin 04/2012; 35(1):89-94. · 0.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We studied the level of noradrenaline and the density of α2-and β-adrenoreceptors in the brain stem and cerebral cortex of
12-day- and 21-day-old rat fetuses, as well as of rats at the ages of 1, 2, 5, 7, 9, 16, 21, 35, and 70 days. We found a positive
correlation between the level of noradrenaline in the brain stem and the density of β-receptors in the cerebral cortex, and
between the amount of α2- and β-receptors in the cerebral cortex, as well as between the values of each of these indices of
the neurochemical system and body weight. Significant negative correlations (r=−0.72 andr=−0.88, respectively) were found between the amount of α2-adrenoreceptors in the brain stem and the content of noradrenaline
in this brain region, as well as in the cerebral cortex. Explanations of these positive and negative correlations between
the level of noradrenaline and the amount of adrenergic receptors in the rat brain during ontogenesis are discussed.
Russian Journal of Developmental Biology 04/2012; 31(1):43-46. · 0.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Changes in gene expression of the brain serotonin (5-HT) 1A receptors may be important for the development and ameliorating depression, however identification of specific stimuli that activate or reduce the receptor transcriptional activity is far from complete. In the present study, the forced swim test (FST) exposure, the first stress session of which is already sufficient to induce behavioral despair in rats, significantly increased 5-HT1A receptor mRNA levels in the brainstem, frontal cortex, and hippocampus at 24 h. In the brainstem and frontal cortex, the elevation in the receptor gene expression after the second forced swim session was not affected following chronic administration of fluoxetine, while in the cortex, both control and FST values were significantly reduced in fluoxetine-treated rats. In contrast to untreated rats, no increase in hippocampal 5-HT1A receptor mRNA was observed in response to FST in rats chronically treated with fluoxetine. Metabolism of 5-HT (5-HIAA/5-HT) in the brainstem was significantly decreased by fluoxetine and further reduced by swim stress, showing a certain degree of independence of these changes on 5-HT1A receptor gene expression that was increased in this brain region only after the FST, but not after fluoxetine. FST exposure also decreased the brainstem dopamine metabolism, which was unexpectedly positively correlated with 5-HT1A receptor mRNA levels in the frontal cortex. Together, these data suggest that the effects of the forced swim stress as well as fluoxetine involve brain region-dependent alterations in 5-HT1A receptor gene transcription, some of which may be interrelated with concomitant changes in catecholamine metabolism.
Cellular and Molecular Neurobiology 03/2012; 32(5):787-94. · 1.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Administration of clonidine, an agonist of alpha2-adrenoceptors at a dose of 0.4 mg/kg to a 3-day-old rat pups decreased the
amount of proapoptotic protein Bax mRNA in the hippocampus and increased the content of antiapoptotic protein Bcl-XL mRNA in the brainstem 120 h after treatment. Administration of yohimbine, an antagonist of alpha2-adrenoceptors, at a dose
of 2 mg/kg increased the level of Bcl-XL mRNA in the hippocampus at the same time point. These effects were specific for each drug. However, both these substances
decreased the amount of mRNAs of Bax and the key executive apoptotic protease, caspase-3, in the cerebral cortex 24 and 120
h after treatment, respectively. Similar effects of clonidine and yohimbine suggest that the effect of the antagonist of alpha2-adrenoceptors
was possibly mediated by endogenous norepinephrine released in response to the antagonist. These results may explain the neuroprotective
features of agonists and antagonists of alpha2-adrenoceptors, which have been previously reported.
Neurochemical Journal 11/2008; 2(4):265-269. · 0.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme in 5-HT synthesis in the brain, is a candidate for participation in a mechanism mediating the antidepressant effect of selective 5-HT reuptake inhibitors such as fluoxetine. Using real-time reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative RT-PCR techniques, we have examined the effects of fluoxetine administration with drinking water (7.5 mg/kg/day) for 2, 4 and 8 weeks on TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus (DRN) and in the brainstem containing the rest of the raphe complex. Fluoxetine treatment for 4 and 8 weeks significantly increased basal TPH2 mRNA levels in the midbrain, an effect that was correlated with the appearance of antidepressant-like effects in the forced swim test. A significant induction of TPH2 and 5-HT transporter (5-HTT) mRNAs was detected in the midbrain of untreated rats 24 h after the swim test. In these animals, the swim test also produced a marked decrease in 5-HT metabolite (5-hydroxyindoleacetic acid (5-HIAA)) content in the amygdala. Fluoxetine treatment for 4 and 8, but not for 2 weeks, abolished these swim-induced changes in TPH2 and 5-HTT mRNAs levels in the midbrain and 5-HIAA content in the amygdala. The results of the present study suggest that TPH2 gene expression in the midbrain part of the DRN is implicated in depression and stress response, as well as in the antidepressant fluoxetine action.
Neuroscience 01/2008; 150(2):404-12. · 3.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Selective serotonin (5-HT) reuptake inhibitors such as fluoxetine are widely used in the treatment of depression and anxiety; however, the mechanisms underlying their action and particularly the delay in therapeutic onset remain unclear. It is proposed that 5-HT reuptake inhibitors exert their therapeutic activity by increasing serotonergic neurotransmission; therefore, the aim of the present study was to investigate the effects of repeated treatment with fluoxetine (25 mg/kg/day p.o., 14 days) on expression of genes coding for proteins that involved in the synthesis and reuptake of 5-HT. Exposure of animals to plus-maze conditions on the first day of drug administration produced an increase in baseline anxiety on subsequent trial 2 weeks later. Fluoxetine strengthened the anxiogenic effects of maze experience. Two-week fluoxetine treatment also significantly reduced expression of tryptophan hydroxylase-2 (TPH2) and 5-HT transporter mRNAs as determined by RT-PCR in the brainstem. These changes were consistent with the decreased 5-HT levels and 5-HT turnover in the brain, and might contribute to the anxiogenic effects of the drug. The results also suggest that recently found association between treatment responses to fluoxetine and polymorphic variants of human TPH2 gene [Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP. Investigation of serotonin-related genes in antidepressant response. Mol Psychiatry 2004; 9:879-889] may be related to the drug effect on the TPH2 gene expression.
Pharmacology Biochemistry and Behavior 10/2006; 85(1):220-7. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effects of the serotonin reuptake inhibitor fluoxetine (FL) and its complexes with glycyrrhizic acid (GA) in molar ratios of 1:1 (FLG-1) and 4:1 (FLG-4) on the behavior of adult rats were studied in an elevated cross maze, with measurement of brain monoamine and monamine metabolite levels. Agents were given via the intragastric route using a cannula at a dose of 25 mg/kg 1 h before testing. FL increased anxiety in the rats and decreased their movement activity; FLG-1 and FLG-4 had no effect on behavior. None of the agents affected brain serotonin content, though all decreased the levels of its metabolite 5-hydroxyindoleacetic acid in the hypothalamus, FLG-4 also decreasing this in the cortex. Noradrenaline levels in the hypothalamus were increased after FLG-1 and FLG-4. In the striatum, FL increased the levels of dopamine and its metabolite dihydroxyphenylacetic acid but had no effect on the level of transmitter catabolism. Unlike FL, FLG-1 activated dopamine metabolism in the striatum. Overall, use of FL complexed with GA significantly modified its behavioral effects, which appears to be associated with the effects of FL and its complexes on the function of the monoaminergic systems involved in controlling behavior.
Neuroscience and Behavioral Physiology 06/2006; 36(4):329-33.
-
[show abstract]
[hide abstract]
ABSTRACT: Bax mRNA level in fetal rat brain stem increases by day 40 of life and then decreases, while level of Bcl-XL mRNA reaches the adult value over one month. Bax mRNA level in the cerebral cortex decreases from day 8 to day 90 of life, while Bcl-XL mRNA level does not change. Judging from Bcl-XL/Bax mRNA ratio, cortical cells exhibit higher readiness to apoptosis than brain stem cells.
Bulletin of Experimental Biology and Medicine 07/2005; 139(6):700-2. · 0.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Bax mRNA level in fetal rat brain stem increases by day 40 of life and then decreases, while level of Bcl-XL mRNA reaches the adult value over one month. Bax mRNA level in the cerebral cortex decreases from day 8 to day 90 of life, while Bcl-XL mRNA level does not change. Judging from Bcl-XL/Bax mRNA ratio, cortical cells exhibit higher readiness to apoptosis than brain stem cells.
Bulletin of Experimental Biology and Medicine 05/2005; 139(6):700-702. · 0.27 Impact Factor
-
Behavioural Pharmacology 08/2004; 15(5-6):A14. · 2.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain development may be involved in early-life programming of anxiety-related behavior.
Neuroscience 02/2004; 129(3):521-8. · 3.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A new method for evaluation of DNA fragmentation in tissue is based on computer-aided densitometric standardization of the sum of optical densities of DNA fragments visualized by electrophoresis (180-2500 b. p.) in comparison with the density of high molecular weight DNA in the same sample. The method allows evaluation of DNA fragmentation, an acknowledged marker of apoptosis, in the fetal rat brain and detection of increased DNA fragmentation during stress and under the effect of glucocorticoids.
Bulletin of Experimental Biology and Medicine 01/2003; 134(6):554-6. · 0.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Androgens are involved in regulation of behaviour through intracellular mechanisms owing to their receptors. Involvement of intercellular messengers such as brain norepinephrine and adrenergic receptors (ARs) is seemed to be necessary to realise hormone-dependent behavioural effects. Castration of adult male rats, which decreases copulatory activity in the animals, was accompanied by a significant increase in 3H-clonidine (alpha2-AR agonist) binding site density in the frontal cortex. The levels of mRNA for the alpha2A-ARs (measured by RT-PCR) were increased in the brainstem of castrated males in parallel to the changes in cortical ARs densities. Testosterone treatment, that activates copulatory behaviour in castrates, down regulated alpha2A-AR mRNA levels in the brainstem and 3H-clonidine binding sites densities in the cortex, where terminals of the brain stem neurones are situated. Unlike in the brainstem, castration caused a decrease in alpha2A-AR mRNA in the cortex and testosterone up-regulated this mRNA in the cortical region. The data suggested that down-regulation of alpha2-ARs densities in the cortex that is induced by testosterone can be preferentially related to alpha2-ARs subpopulation which is expressed by the brainstem neurones and imported into the cortex by axons of these neurones.
Psychoneuroendocrinology 08/2002; 27(5):585-92. · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Antisense strategy was used to investigate the role of alpha2A-adrenoceptor (alpha2A-AR) subtype in anxiety-related behavior. A 18-mer phosphorothioate oligodeoxynucleotide (AS-ODN) complementary to the alpha2A-AR mRNA was administered to the adult male rats for 3 days (1 nmol/5 microl/day) into the region of locus coeruleus (LC). Control groups received infusions of either oligodeoxynucleotide of a random sequence (RS-ODN) or saline. Treatment with AS-ODN significantly reduced the levels of alpha2A-AR mRNA in the brain stem. At the same time, AS-ODN treatment caused only a small reduction in [(3)H]clonidine binding (by 26-32%) in the brain stem which was not significant. Compared to both RS-ODN and saline controls, treatment with AS-ODN significantly increased the percentage of open arm entries in the elevated plus-maze while the total number of arm entries was unaltered. Also, AS-ODN treatment elevated basal levels of plasma corticosterone by 217% and 96% compared to both RS-ODN and saline controls. These changes in the hormone concentrations were at a level of marginal significance (p<0.1 versus random group). Taken together, the data indicate that administration of AS-ODN against alpha2A-ARs in the LC significantly reduced expression of alpha2A-AR mRNA in brain stem, moderately increased plasma corticosterone and had anxiolytic-like effect in the elevated plus-maze.
Psychoneuroendocrinology 07/2002; 27(5):593-601. · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The content of caspase-3 mRNA in rat brain stem decreased from birth to postnatal week 3 and dropped below reverse transcription-PCR sensitivity limit in 1.5-month-old animals. The number of brain stem cells in 2-40-day-old rats was constant. The content of caspase-3 mRNA in the cortex was higher than in the brain stem and decreased by one-third by postnatal day 40. The number of cells in the cortex decreased 2-fold during postnatal week 1 and then remained unchanged. Changes in the content of caspase-3 mRNA did not correlate directly with variations in the number of brain cells during postnatal ontogeny.
Bulletin of Experimental Biology and Medicine 09/2001; 132(2):748-50. · 0.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Clinical and experimental findings have implicated brain alpha2-adrenoceptors in the regulation of many physiological functions, including sexual activity and stress-related behavior. However, which subtypes of the three alpha2-adrenoceptors that have now been cloned (alpha2A, alpha2B, and alpha2C) are involved in these controls have yet to be established. Here, we investigated the contribution of alpha2A-adrenoceptors of the locus ceruleus, the principal source of brain noradrenaline, to exploratory and sexual behaviors. Using administration of antisense oligodeoxynucleotide to inhibit the receptor expression, we found that reductions in brainstem alpha2A-adrenoceptor mRNA levels and alpha2-adrenoceptor densities induced by antisense treatment were not accompanied by any changes in the major characteristics of male sexual activity, such as mount latencies and numbers of mounts. However, in sexual behavior tests, antisense-treated male rats had decreased numbers of rearings and thus have higher percentages of behaviors positively correlated with sexual activity. Besides, antisense-treated animals had decreased anxiety in plus-maze tests. The data demonstrate that inhibition of alpha2A-adrenoceptor expression in the region of the locus ceruleus has an anxiolytic-like effect and facilitates male's attention to female in sexual behavior test.
Journal of Neuroscience 02/2001; 21(2):726-31. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Now available nucleotide sequences of neurotransmitter receptor genes enable to apply oligonucleotides targeted to mRNAs of these genes for highly selective inactivation of their expression (antisense-knockdown) and for function determination of single receptor subtype by this experimental approach. The antisense-knockdown may be of special importance in case of receptor families members of which are pharmacologically similar. Advantages of the antisense technology for investigation into the brain neurotransmitter receptor function in regulation of behaviour, are discussed.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 11/2000; 86(10):1278-82.
-
Biulleten' eksperimental'noĭ biologii i meditsiny 01/2000; 128(12):616-8.
-
Doklady Akademii nauk / [Rossiĭskaia akademii nauk] 02/1999; 364(3):417-9.
