RESUMEN
In experiments on rats, we studied the effect of 5-day intraperitoneal (15 mg/kg/day) and oral (40 mg/kg/day) administration of compound TPY3m, a stimulator of the production of thyroid hormones by the thyroid gland developed by us, on the blood levels of thyroxine, triiodothyronine, and thyroid-stimulating hormone and on morphology of the thyroid gland. With both routes of administration, TPY3m caused a sustained moderate elevation of thyroid hormones, mainly thyroxine, with little effect on the level of thyroid-stimulating hormone. TPY3m did not reduce the stimulating effect of thyroliberin on the levels of thyroid hormones and had no damaging effect on the thyroid gland. During long-term administration, compound TPY3m stimulates the production of thyroid hormones without weakening the activity of the thyroid axis. Thus, TPY3m is a prototype of drugs for correcting thyroid hormone deficiency.
RESUMEN
We compared the effectiveness of human chorionic gonadotropin (hCG; 5 days, 20 IU/rat/day), allosteric luteinizing hormone receptor agonist TP04 (5 days, 20 mg/kg/day), and metformin (28 days, 120 mg/kg/day) in restoring spermatogenesis in male rats with type 2 diabetes mellitus. hCG and TP04 increased the levels of testosterone and expression of the steroidogenic protein StAR, the number of spermatogenic cells, thickness of the seminal epithelium, and the number and motility of mature sperm that were reduced in diabetic rats, though they did not reduce the number of defective spermatozoa. Metformin had a weak effect on steroidogenesis, but was not inferior to luteinizing hormone receptor agonist by its restorative effect on spermatogenesis and also reduced the number of defective forms of spermatozoa. Thus, the spermatogenesis-restoring effect of metformin and luteinizing hormone receptor agonist in type 2 diabetes mellitus are comparable, despite different mechanisms of action.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metformina , Animales , Gonadotropina Coriónica/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Metformina/farmacología , Ratas , Receptores de HL/agonistas , Receptores de HL/genética , Receptores de HL/metabolismo , Espermatogénesis , Estreptozocina , Testículo/metabolismo , Testosterona/metabolismoRESUMEN
Human chorionic gonadotropin that is widely used for improving spermatogenesis. The effect of chorionic gonadotropin is mediated through luteinizing hormone receptor. Treatment with gonadotropin is associated with undesirable effects due to hyperactivation of testosterone production and luteinizing hormone receptor desensitization. A promising alternative could be low-molecular-weight agonists of luteinizing hormone receptors, but their effects on spermatogenesis have not been investigated. Here we analyzed the effect of a thieno[2,3-d]pyrimidines (TP), 4-((3-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno [2,3-d]pyrimidine-4-yl) phenyl)carbamoyl)pyridine 1-oxide (TP22), an allosteric agonist of luteinizing hormone receptors, on the seminiferous tubules and spermatogenic cells in 4- and 18-month-old male rats and in animals with diabetes mellitus. TP22 and gonadotropin were administered in daily doses of 15 mg/kg and 20 U/rat for 5 days. Blood testosterone level, morphology of the seminiferous tubules, and the number of germ cells in them were estimated. Being comparable by the efficiency to gonadotropin, TP22 increased the testosterone level in all the studied groups of rats and restored epithelium thickness in the seminiferous tubules and the number of spermatogonia and pachytenic spermatocytes that are reduced in aging and diabetes, but, unlike gonadotropin, did not suppress the expression of luteinizing hormone receptor. The efficacy of TP22 as a stimulator of testicular spermatogenesis has been demonstrated both under normal conditions and in age-related and diabetes-associated reproductive dysfunctions.
Asunto(s)
Diabetes Mellitus Experimental , Receptores de HL , Envejecimiento , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Hormona Folículo Estimulante/metabolismo , Masculino , Ratas , Receptores de HL/agonistas , Receptores de HL/metabolismo , Espermatogénesis , Testículo/metabolismo , TestosteronaRESUMEN
In recent years, the effectiveness of high-dose metformin (MF) to treat the endocrine and oncological diseases has been shown. However, the use of high-dose MF may be associated with the lactic acidosis and the liver dysfunctions. The aim of the work was to study the effect of long-term (10 days) oral administration of a relatively high dose of MF (600 mg/kg per day) into yellow C57Bl/6J (Ay/a) Agouti line mice with the melanocortin type obesity on the liver function, which was evaluated by the morphology of hepatocytes and the severity of steatosis, the expression of the inflammatory and apoptotic factors of and the activity of aminotransferases, as well as on the plasma lactate level in the animals. In Agouti line mice, MF (600 mg/kg per day) caused a decrease in the body and fat weight, led to the reduced hyperglycemia, hyperinsulinemia and hyperleptinemia, and restored the sensitivity to glucose and insulin. At the same time, in the liver of Agouti line mice treated with MF, the small-drop and large-drop fatty degeneration and the hydropic degeneration were attenuated, and the expression of pro-inflammatory IL-1ß and pro-apoptotic Bax protein and the Bax/Bcl-2 ratio did not differ from the control C57Bl/6J (a/a) mice. In the blood of Agouti line mice treated with MF, the activity of alanine aminotransferase was normalized, and the lactate levels was increased, but to a moderate degree. It was concluded that the high-dose MF did not induce the lactic acidosis in Agouti line mice, and at the same time it restored the liver functions impaired in the melanocortin obesity. This allows us to consider the use of the high doses of MF as one of the possible ways to treat obesity and metabolic disorders that are associated with the hepatic steatosis.
Asunto(s)
Hígado , Melanocortinas , Metformina , Obesidad , Animales , Ratones , Hígado/efectos de los fármacos , Melanocortinas/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/fisiopatologíaRESUMEN
Using immunofluorescent techniques, we have demonstrated the presence of two main types of dopamine receptors, D1 and D2, on the bodies of neurons of the arcuate nucleus of the hypothalamus expressing the precursor of peptides of the melanocortin family proopiomelanocortin in C57Bl/6J mice and Wistar rats. These data show close functional relationship between the dopamine and melanocortin systems of the brain and involvement of dopamine in the control of synthesis and secretion of peptides of the melanocortin family.
Asunto(s)
Núcleo Arqueado del Hipotálamo , Regulación de la Expresión Génica/fisiología , Neuronas , Proopiomelanocortina/biosíntesis , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animales , Núcleo Arqueado del Hipotálamo/citología , Núcleo Arqueado del Hipotálamo/metabolismo , Masculino , Ratones , Neuronas/citología , Neuronas/metabolismo , Ratas , Ratas WistarRESUMEN
The metabolic parameters and functional state of hypothalamic systems in mice with the Yellow mutation in the Agouti locus and with obesity of the melanocortin type and the effect of metformin (MF) treatment (9 days, 200 mg/kg/day) were studied. The MF treatment led to decreased body weight and to normalization of glucose tolerance in mice. In the hypothalamus, MF restored the decreased activity of Akt kinase, the main component of leptin pathway, and normalized the increased expression of subtype 1B serotonin receptor. The obtained data suggest the efficiency of MF to treat obesity of the melanocortin type.
Asunto(s)
Predisposición Genética a la Enfermedad , Hipotálamo , Metformina/farmacología , Metformina/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/genética , Animales , Hipotálamo/efectos de los fármacos , Ratones , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
The brain melanocortin system plays a key role in the regulation of energy metabolism and feeding behavior and is involved in memory formation, and its abnormalities lead to metabolic disorders and cognitive deficit. The brain dopamine system controls the motor activity, the functions of the nervous, endocrine and cardiovascular systems, and is also involved in the regulation of peripheral metabolism and feeding behavior and in the formation of effect of reward and reinforcement. The fact that a large number of the important physiological functions are controlled by the melanocortin and dopamine systems indicates a close functional relationship between them in different areas of the brain. The basis of this relationship is colocalization of the components of melanocortin and dopamine signaling systems in neurons and interaction between them, which ensures a cross-talk between melanocortin and dopamine pathways in the CNS. The review includes a comprehensive analysis of the current state of the problem concerning the interaction between the melanocortin and dopamine systems of the brain at both the structural and functional levels.
Asunto(s)
Encéfalo/metabolismo , Dopamina/metabolismo , Metabolismo Energético/fisiología , Conducta Alimentaria/fisiología , Actividad Motora/fisiología , Transducción de Señal/fisiología , Animales , Neuronas Dopaminérgicas/metabolismo , HumanosRESUMEN
There are obtained data indicating that morphogenesis and, probably, formation of structurally functional interaction of the CART- and dopaminergic neurons occur as early as during embryonic development. Meanwhile development of the AGRergic system and formation of its structural and functional communications are observed in the course of postnatal development of rat. Analysis of literature and re- sults of our own investigation show that differentiation of dopaminergic neurons in hypothalamus and midbrain occurs on the background of development of CARTergic neurons and in the absence of AGRP. Taking into account our data on activating action of the CART-peptide and inhibitory effect of AGRP on dopaminergic brain neurons, we believe that the leading component at formation of functional interactions of these systems is the later maturing AGRPergic system.
Asunto(s)
Proteína Relacionada con Agouti/metabolismo , Neuronas Dopaminérgicas/fisiología , Hipotálamo/fisiología , Mesencéfalo/fisiología , Proteínas del Tejido Nervioso/metabolismo , Neurogénesis , Proteína Relacionada con Agouti/genética , Animales , Neuronas Dopaminérgicas/citología , Neuronas Dopaminérgicas/metabolismo , Hipotálamo/citología , Hipotálamo/embriología , Mesencéfalo/citología , Mesencéfalo/embriología , Proteínas del Tejido Nervioso/genética , Ratas , Ratas WistarRESUMEN
For the first time, the biodistribution of recombinant heat shock protein in rhHsp70 rats with grafted intracranial C6 glioma was evaluated. It was assessed using the fluorescent antibody accumulation chaperone rhHsp70 conjugated with fluorochrome Alexa Fluor 555 in tumor cells by intratumoral or intravenous administration. Assessment of the distribution and accumulation of labeled protein was carried out on the model of subcutaneous B16/F10 melanoma in C57BL/6 mice with the use of single-photon emission computer tomography. After 60 minutes after intravenous administration rhHsp70-I123 (20 MBq, 5 mg chaperone) accumulation of the drug mainly in the liver and tumor tissue was showed. The coefficient of the differential accumulation of the labeled protein KDN(tumor/background) was 3.14. It was turned out that comparing the level of fixation of rhHsp70-I123 in the liver and the tumor KDN(tumor/ liver) = 0.76. After 24 hours from the time of injection of rhHsp70-I123 it was observed increase the level of fixation of the labeled protein in the liver and melanoma: KDN(tumor/background) = 3.43; KDN(tumor/liver = 0.78.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Hígado/metabolismo , Melanoma Experimental/metabolismo , Neoplasias Cutáneas/metabolismo , Animales , Colorantes Fluorescentes , Proteínas HSP70 de Choque Térmico/administración & dosificación , Proteínas HSP70 de Choque Térmico/farmacocinética , Inyecciones Intralesiones , Inyecciones Intravenosas , Radioisótopos de Yodo , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
In Wistar rats, after 6 h of sleep deprivation and subsequent 2 h postdeprivation sleep, we found significant changes in optical density of CART-peptide in neurons of hypothalamic nucleus accumbens and nucleus arcuatus as well as in processes coming into substantia nigra from nucleus accumbens. The obtained data revealed unidirectional changes of optical density of tyrosine hydroxylase: a decrease after sleep deprivation (p < 0.05) and, on the contrary, an increase on the background of postdeprivation sleep (p < 0.05). Confocal laser microscopy showed morphological connections of CART and dopaminergic neurons and possible colocalization of these both substances in the same neuron at the postdeprivation sleep. In experiments in vitro, after 1 h of incubation of survived brain slices from the substantia nigra area in the medium with CART-peptide there was revealed a rise of optical density of tyrosine hydroxylase in the substantia nigra compact part by 55 % (p < 0.05). The obtained data indicate an activating effect of CART-peptide on brain dopaminergic neurons and its as a modulator of their functional activity.
Asunto(s)
Neuronas Dopaminérgicas , Proteínas del Tejido Nervioso/metabolismo , Privación de Sueño , Sustancia Negra , Animales , Núcleo Arqueado del Hipotálamo/metabolismo , Núcleo Arqueado del Hipotálamo/fisiología , Mapeo Encefálico , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/fisiología , Masculino , Núcleo Accumbens/metabolismo , Ratas , Ratas Wistar , Sustancia Negra/metabolismo , Sustancia Negra/fisiología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
In rats and mice in different dopaminergic brain structures the immunoreactive axons with agouti-related protein (AGRP) were identified. The double immunofluorescence method shows the presence of AGRP-immunoreactive processes around the bodies of dopaminergic neurons. In experiments in vitro after incubation of brain tissue from ventral tegmental area or hypothalamus with AGRP (83-132) the significant decrease of tyrosine hydroxylase optical density was indicated. The data indicate possible direct inhibitory action of AGRP on tyrosine hydroxylase level in dopaminergic brain neurons and its role as a modulator of the functional activity of dopaminergic neurons.
Asunto(s)
Proteína Relacionada con Agouti/administración & dosificación , Neuronas Dopaminérgicas/ultraestructura , Hipotálamo/metabolismo , Tirosina 3-Monooxigenasa/biosíntesis , Animales , Axones/metabolismo , Axones/ultraestructura , Dopamina/metabolismo , Hipotálamo/ultraestructura , Mesencéfalo/metabolismo , Mesencéfalo/ultraestructura , Ratones , RatasRESUMEN
Agouti-related protein (AGRP) is expresses in hypothalamic neurons in human and animals. Immunohistochemical study in rats Wistar rats demonstrates significant changes AGRP optical density in the neurons of arcuate hypothalamic nucleus as well as in processes in the hypothalamus and nucleus accumbens after the 6 hours of sleep deprivation (increase) and after 2 hours of post-deprivative sleep (decrease). Comparison of these results with earlier obtained shows the opposite trend changes in AGRP optical density and speed limiting enzyme of dopamine synthesis-tyrosine hydroxylase in the hypothalamus and in striatonigral system. The increase of AGRP was accompanied by a decrease of tyrosine hydroxylase and the decrease of AGRP, apposite, it increases. The obtained data demonstrate the role ofAGRP as a modulator of the functional activity of the dopaminergic brain neurons. The problem of the relationship of various functions of organism (food behavior, sleep, stress) is discusses by their participation in the regulation of the same neurotransmitter systems.
Asunto(s)
Proteína Relacionada con Agouti/metabolismo , Neuronas Dopaminérgicas/metabolismo , Hipotálamo/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Núcleo Accumbens/metabolismo , Sueño/fisiología , Animales , Dopamina/metabolismo , Neuronas Dopaminérgicas/citología , Humanos , Hipotálamo/citología , Masculino , Núcleo Accumbens/citología , Ratas , Ratas WistarRESUMEN
The increase of CART-peptide optical density was found immunohistochemically in nucleus accumbens neurons and in their terminals in substantia nigra in Wistar rats after 28% reduction of dopaminergic neurons in a substantia nigra (in the model of lactacystin induced proteo some disfunction). At the same time after in vitro incubation of nigro-accumbal brain slice with AMPT (alpha-methyl-paratirosine--dopamine inhibitor) for 4 h the reduction of tyrosine hydroxylase optical density (the enzyme limiting dopamine synthesis) in substantia nigr neurons was found and optical density of CART-peptide in nucleus accumbens and substantia nigra was also revealed. In both experiments data about activation of CARTergic neurons in stria to-nigral projections testifies on participation of CART-peptide in compensatory brain mechanisms at dopamine loss and its role as modulator of dopaminergic brain neurons functional activity.
Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina , Neuronas Dopaminérgicas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Fragmentos de Péptidos/metabolismo , Sustancia Negra/metabolismo , Acetilcisteína/análogos & derivados , Acetilcisteína/farmacología , Animales , Cuerpo Estriado/citología , Inhibidores de Cisteína Proteinasa/farmacología , Neuronas Dopaminérgicas/citología , Inmunohistoquímica , Masculino , Núcleo Accumbens/citología , Núcleo Accumbens/metabolismo , Ratas , Ratas Wistar , Sustancia Negra/citología , alfa-Metiltirosina/farmacologíaRESUMEN
Clock-gene proteins are expressed in mammals in neurons of the hypothalamus suprachiasmatic nucleus and of other CNS structures, in muscles, viscercal organs, and vessels, and form circadian rhythms of many functions. Little is known about the factors of formation of the circadian mechanism at the prenatal period. In rats the E20 stage is characterized by a high level of oxytocin and selective expression of the first protein of the clock-genes PER1. The foal of the present study was to check the suggestion about the positive feedback between PER1 and oxytocin at the prenatal period as well as to elucidate a possible role of PER1 in regulation of interactions between oxytocin and GABA at the period of formation of the cerebral circadian mechanism of clock-genes. With aid of western-blotting, we analyzed the nuclear and cytoplasmic fractions from anterior hypothalamus homogenate in pregnant females and embryos of rats (E20). The retinol metabolites through their nuclear receptor RORalpha are known to be bound to promoters of genes of oxytocin and per 1. Next day after administration of retinol to the females, a rise of PER1 content was noted in their cytoplasm, whereas in their embryos the PER1 content was elevated in the nucleus. In the embryo cytoplasm there was a significant rise of production of oxytocin receptors and a decrease of the level of enzymes of GABA synthesis (glutamate decarboxylases 67 and 65). The results indicate the oxytocin- and retinol-dependent increase of the PER1 expression and the subsequent change of ratio of efficiency of oxytocin and GABA at the prenatal stage of formation of the circadian clock-mechanism of the rat embryo anterior hypothalamus.
Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Embrión de Mamíferos/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Oxitocina/metabolismo , Proteínas Circadianas Period/biosíntesis , Vitamina A/farmacología , Vitaminas/farmacología , Ácido gamma-Aminobutírico/metabolismo , Animales , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Hipotálamo Anterior/embriología , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Embarazo , Ratas , Factores de TiempoRESUMEN
Molecular chaperons can effectively activate innate and adaptive anti-tumor immune response. In the model of intracranial glioma C6 in Wistar rats we assessed immunomodulatory activity of recombinant protein Hsp70 in case of local, intratumoral injection. Single intratumoral infusion of chaperone had led to dramatic delay in tumor volume growth (on MRI of rat brain), which was accompanied by increase in survival rates. Incubation of rat spleenocytes with C6 cells elevated the levels of INF-gamma, that shows an immunologically specific T-cell response. With immunohistochemical assay we observed a marked infiltration of the tumor by T-lymphocytes and NK-cells. Thus, purified Hsp70 can efficiently induce innate and adaptive anti-tumor response and could be used as adjuvant in treatment of malignant brain tumors of central nervous system.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/inmunología , Glioblastoma/tratamiento farmacológico , Glioblastoma/inmunología , Proteínas HSP70 de Choque Térmico/farmacología , Inmunidad Adaptativa/efectos de los fármacos , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Antineoplásicos/administración & dosificación , Modelos Animales de Enfermedad , Proteínas HSP70 de Choque Térmico/administración & dosificación , Inmunidad Innata/efectos de los fármacos , Infusiones Intralesiones , Interferón gamma/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Ratas , Ratas Wistar , Proteínas Recombinantes/farmacología , Análisis de Supervivencia , Linfocitos T/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
In Drosophila, juvenile hormone (JH) is synthesized de novo in the specialized endocrine gland, corpusallatum (CA). Dopamine (DA) controls JH levels by either stimulating or inhibiting its synthesis and degradation depending on the developmental stage. The present study focuses on the role of D2-like receptors in the regulation of JH synthesis by dopamine. We show that D2-like receptors (DD2R) are expressed in CA cells of Drosophila melanogaster females. In addition, the level of JH production was analyzed in D. melanogaster females with decreased DD2R expression in CA (vs. corresponding control flies) by assessing multiple indices of JH synthesis (JH-hydrolyzing activity and stress reactivity of the system of JH metabolism, activity and stress reactivity of the alkaline phosphatase, activity and stress reactivity of the tyrosine decarboxylase). The differential value obtained for each index suggests increased JH production in female flies that downregulate DD2R. Based on these findings, we postulate that the DA inhibiting effect on the JH synthesis in D. melanogaster is mediated at least in part via D2-like receptors.
Asunto(s)
Corpora Allata/metabolismo , Dopamina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Hormonas Juveniles/biosíntesis , Receptores de Dopamina D2/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Animales Modificados Genéticamente , Regulación hacia Abajo , Femenino , Respuesta al Choque Térmico , Tirosina Descarboxilasa/metabolismoRESUMEN
Previous studies have shown that juvenile hormone (JH) regulates dopamine (DA) and octopamine (OA) content in Drosophila, and we have shown the influence of an increase in JH level on DA and OA metabolism in young females of Drosophila virilis and Drosophila melanogaster. Here we investigate the effects of genetic ablation of a subset of cells in the Corpusallatum (CA, endocrine gland synthesizing JH) on the DA levels and activities of alkaline phosphatase (ALP), tyrosine hydroxylase (TH), DA-dependent arylalkylamine N-acetyltransferase (DAT) and tyrosine decarboxylase (TDC) in young D. melanogaster females under normal conditions and upon heat stress (38°Ð¡). We show that ablation of СРcells causes: (1) a decrease in ALP, TH and DAT activities, (2) an increase in DA level and (3) an increase in TDC activity in young females. The CA ablation was also found to modulate ALP, TH and TDC responses to heat stress. Mechanisms of regulation of DA and OA levels by JH in Drosophila females are discussed.
Asunto(s)
Dopamina/biosíntesis , Drosophila melanogaster/metabolismo , Hormonas Juveniles/metabolismo , Octopamina/biosíntesis , Estrés Fisiológico , Fosfatasa Alcalina/metabolismo , Animales , N-Acetiltransferasa de Arilalquilamina/metabolismo , Corpora Allata/citología , Corpora Allata/fisiología , Drosophila melanogaster/genética , Femenino , Calor , Tirosina 3-Monooxigenasa/metabolismo , Tirosina Descarboxilasa/metabolismoRESUMEN
Six hours sleep deprivation experiments were carried out on rats after threefold injection of D1 dopamine receptor antagonist SCH 39 166. Immunohistochemical study of striatum revealed the increase in D1 and D2 dopamine receptor and glutamate immunoreactive material during the sleep deprivation and 2 h of postdeprivation period. The level of AMPA glutamate receptors increased under the sleep deprivation and decreased in the postdeprivation period. The data obtained are discussed in association with dynamic of changes of vasopressin immunoreactivity in neurosecretory supraoptical and paraventricular nuclei of hypothalamus in these experiments and in experiments without D1 receptor antagonist pretreatment.
Asunto(s)
Benzazepinas/farmacología , Antagonistas de Dopamina/farmacología , Receptores AMPA/metabolismo , Privación de Sueño/metabolismo , Vasopresinas/metabolismo , Animales , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/fisiopatología , Ratas , Ratas Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Privación de Sueño/fisiopatología , Núcleo Supraóptico/metabolismo , Núcleo Supraóptico/fisiopatologíaRESUMEN
The comparative immunohistochemical researches of dofamine containing neurons and fibers are carried uot in telencephalic and diencephalic departments of the brain in different vertebratts (adults rats, rats aged 14 and 30 days and frogs). For analysis of quantitative changes dynamics in thyrozinhydroxylase, D1 and D2 immunoreactive material in sleep-wakefulness cycle the model of sleepdeprivation is used. There are found the facts of morphofunctional correlations in the reactions of dophaminergic system during ontogeny and phylogeny. Besides, the pharmacological effects of dofamine agonist and antagonists on the sleep-wakefulness cycle in young rats and in frogs are shown. So, dopamine and its agonist apomorphine increase in sleep-wakefulness cycle duration of sleep-like state ofcataplexy (homolog of the sleep) in frogs, in 30-day-old rats it increase the share of wakefulness and catalepsy. D1 receptors antagonist (SCH 23390) adminisrated to frogs, caused increase of wakefulness and catatonic type states duration, where as D2 receptors antagonist (apomorphine) increased cataleptic condition. Administration of dopamine antagonist (haloperidol) to 30-day-old rats previously causes the increase of cataleptic state, after which the slow wave sleep state is enhanced. The questions of phylo-, ontogenetic formation of dopaminergic system regulating role in sleep-wakefulness cycle, when transition mainly from neurosecretory diencephalic influences of dophamine to the mainly neurotransmittory functins of telencephalic regions occured, is discussed.