The Effects of Hypothyroidism on 5-HT1A and 5-HT2A Receptors and the Serotonin Transporter Protein in the Rat Brain

The effects of hypothyroidism on 5-HT_1A and 5-HT_2A receptors and the serotonin transporter protein were studied in thyroidectomized male Wistar rats in two experimental groups: 1) animals kept on an iodine-free diet (hypothyroid rats) and 2) animals kept on thyroxine (15 g/kg) for 21 days (giving normal thyroid hormone levels, euthyroid animals). Sham-operated rats served as controls. Binding of [³H]8-OH-DPAT with 5-HT_1A receptors and [³H]citalopram with the transporter protein in the hippocampus and midbrain showed no changes in hypothyroid rats as compared with controls. Conversely, there were significant decreases in [³H]ketanserin binding to 5-HT_2A receptors in the frontal cortex in hypothyroid rats as compared with controls; this decrease was reversed by thyroxine treatment. Thus, losses of cortical 5-HT_2A receptors appears to be the main consequence of hypothyroidism at the level of the serotonin system of the brain.     

Effects of an Agonist and an Antagonist of 5-HT1A Serotonin Receptors on Learning in Female Rats during the Ovarian Cycle

The experiments reported here addressed comparative analysis of the role of 5-HT_1A serotonin receptors in the mechanisms mediating cognitive processes during natural cyclical changes in sex hormone levels in adult female rats. The effects of chronic (14 days) administration of the 5-HT_1A serotonin receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and the 5-HT_1A serotonin receptor antagonist NAN-190 (0.1 mg/kg, i.p.) to females at different phases of the ovarian cycle on conditioned reflex responses were studied. A conditioned passive avoidance reaction and the Morris water maze were used as behavioral tests. Chronic administration of NAN-190 to females led to the appearance of the conditioned passive avoidance response in the proestrus and estrus phases, in contrast to control females, but had no effects on the dynamics of spatial learning in the Morris water test. Chronic administration of 8-OH-DPAT consistently impaired the processes of non-spatial and spatial learning in females regardless of the phase of the ovarian cycle. The results obtained in these experiments evidenced the modulatory role of 5-HT_1A serotonin receptors in learning processes in rats in key phases of the ovarian cycle.     

高效毛细管电泳法分离多巴胺和5-羟色胺

建立毛细管电泳分离分析多巴胺和 5一羟色胺的方法。采用自由区带电泳法 (CZE) ,4 0mmol/L硼砂缓冲液 2 0PSI气压进样 5s ,定电流 75 μA分离 10min ,二极管阵列PDA检测器检测 ,应用 2 0 0nm检测波长 ,结果显示两种物质完全分离。     

Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors

Serotonin(1A)-receptors (5-HT(1A)-Rs) are important components of the 5-HT system in the brain. As somatodendritic autoreceptors they control the activity of 5-HT neurons, and, as postsynaptic receptors, the activity in terminal areas. Cocaine (COC), amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine ("Ecstasy", MDMA) are psychostimulant drugs that can lead to addiction-related behavior in humans and in animals. At the neurochemical level, these psychostimulant drugs interact with monoamine transporters and increase extracellular 5-HT, dopamine and noradrenalin activity in the brain. The increase in 5-HT, which, in addition to dopamine, is a core mechanism of action for drug addiction, hyperactivates 5-HT(1A)-Rs. Here, we first review the role of the various 5-HT(1A)-R populations in spontaneous behavior to provide a background to elucidate the contribution of the 5-HT(1A)-Rs to the organization of psychostimulant-induced addiction behavior. The progress achieved in this field shows the fundamental contribution of brain 5-HT(1A)-Rs to virtually all behaviors associated with psychostimulant addiction. Importantly, the contribution of pre- and postsynaptic 5-HT(1A)-Rs can be dissociated and frequently act in opposite directions. We conclude that 5-HT(1A)-autoreceptors mainly facilitate psychostimulant addiction-related behaviors by a limitation of the 5-HT response in terminal areas. Postsynaptic 5-HT(1A)-Rs, in contrast, predominantly inhibit the expression of various addiction-related behaviors directly. In addition, they may also influence the local 5-HT response by feedback mechanisms. The reviewed findings do not only show a crucial role of 5-HT(1A)-Rs in the control of brain 5-HT activity and spontaneous behavior, but also their complex role in the regulation of the psychostimulant-induced 5-HT response and subsequent addiction-related behaviors.     

Postmating Change in Physiology of Male Drosophila Mediated by Serotonin (5-HT)

Abstract:

Sex peptides transferred during mating from male to female fly profoundly influence the female's behavior and physiology, including an increase in the movement of eggs along the oviduct. In the male ejaculatory duct, the authors have identified peristaltic waves that travel distally with an average frequency of 0.6 Hz. The frequency of peristalsis is increased by 0.1 μM serotonin (5-HT) and completely blocked by 5-HT antagonists (IC₅₀< 1 μM). The authors also report that mating affects the male reproductive tract; peristaltic waves along the ejaculatory duct are significantly reduced postcopulation by 30%. Serotonergic neurons innervate the ejaculatory duct, but their genetic ablation does not prevent peristalsis. The authors propose that peristalsis may be modulated by serotonin circulating in the hemolymph. As serotonin is linked with attentiveness in both flies and mammals, this bioassay suggests reduced behavioral sensitivity of the male fly after mating.     

The Role of Serotonin Receptors in Delta-Opioid Immunosuppression

Studies in CBA mice and Wistar rats demonstrated the involvement of serotonin (5-HT) receptors in immunosuppression evoked using the selective δ2 opioid receptor (δ2-OR) agonist DSLET (100 μg/kg). This opioid effect was seen in conditions of selective activation of 5-HT_1A autoreceptors with 8-OH-DPAT (0.1 mg/kg) and in conditions of prior blockade of postsynaptic 5-HT_1A and 5-HT_2A receptors with WAY-100635 and ketanserin (1 and 3 mg/kg). The question of the different contributions of these types of 5-HT receptor to δ-induced suppression of the immune response is discussed.     

Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum

Although serotonin (5-hydroxytryptamine, 5-HT) is known to exert a modulatory action on cerebellar function, our current knowledge of the nature of receptor subtypes mediating serotonergic activity in this part of the brain remains fragmentary. In this study, we report the presence and distribution of 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum using immunofluorescence histochemistry. 5-HT3 immunoreactivity was found in fibers sparsely distributed throughout the cerebellum. Most of them were seen in the cerebellar cortex as fine varicose 5-HT3-positive axonal processes. 5-HT5A immunoreactivity, on the other hand, was observed in neuronal somata of the cerebellar cortex and deep cerebellar nuclei. Based upon cell morphology and the use of cell-specific markers, Purkinje cells, molecular layer interneurons and Golgi cells were found to be 5-HT5A immunopositive. In addition, the use of cell-specific markers allowed us to identify previously reported large 5-HT2A-positive cells in the granular layer as being Golgi cells. Finally, 5-HT7 immunoreactivity was observed only in Purkinje cells. Corroborating previous radioligand-binding, in situ hybridization and immunohistochemical studies, our data relate serotonin receptor subtypes to specific cerebellar cell types and may consequently contribute to the elucidation of serotonergic actions in the cerebellum.     

Serotonin inhibits apoptosis of pulmonary artery smooth muscle cell by pERK1/2 and PDK through 5-HT1B receptors and 5-HT transporters

BackgroundDecreased apoptosis of pulmonary artery smooth muscle cells (PASMCs) plays a key role in pulmonary vascular remodeling in pulmonary hypertension (PH). However, the cause and mechanism of this decrease in apoptosis are still unclear. Serotonin (5-HT) has been shown to be involved in PH by inducing PASMC proliferation through the activation of 5-HT_1B receptors (5-HT_1BR) and 5-HT transporter (5-HTT). 5-HT_1BR and 5-HTT are also involved in abnormal apoptosis in many other pathological processes. Therefore, we hypothesized that 5-HT induces decreases in PASMC apoptosis through 5-HT_1BR and 5-HTT.MethodsPASMCs were treated with 5-HT, and their proliferation and apoptosis were assayed. 5-HT_1BR agonists, 5-HT_1BR antagonist, 5-HTT antagonist, combined 5-HT_1BR/5-HTT antagonists, extracellular signal-regulated kinase (ERK1/2) activation inhibitor peptide I (EPI) and pyruvate dehydrogenase kinase (PDK) inhibitor sodium dichloroacetate (DCA) were used to explore the mechanism by which 5-HT induce decrease in PASMC apoptosis.ResultsPASMCs stimulated by 5-HT showed an increase in proliferation and a decrease in apoptosis, accompanied by increase in pERK1/2, PDK, and mitochondrial transmembrane potential. The effects of 5-HT on the proliferation and apoptosis of PASMCs were similar to those of 5-HT_1BR agonists and were markedly prevented by 5-HT_1BR antagonist, 5-HTT antagonist, combined 5-HT_1BR/5-HTT antagonists, EPI, or DCA.Conclusions5-HT inhibits PASMC apoptosis through 5-HT_1BR or 5-HTT. pERK1/2 and PDK are involved in the process of 5-HT inhibition PASMC apoptosis through 5-HT_1BR or 5-HTT.     

The 5-HTTLPR Polymorphism of the Serotonin Transporter Gene and the Intellectual Environment of Work Activity as Factors Associated with Changes to Memory in Aging

Neuroscience and Behavioral Physiology - The heterogeneity of mental aging is due to the influences of both genetic and environmental factors. Among the latter, an important role is played by...     

Prenatal Stimulation of 5-HT1A Receptors Improves Adaptive Behavior in Prenatally Stressed Rats

Bulletin of Experimental Biology and Medicine - Various types of adaptive behavior during the prepubertal period were analyzed in the offspring of rats receiving chronic injections of serotonin...     

Serotonin (5-hydroxytryptamine, 5-HT) immunoreactive endocrine and neural elements in the chromaffin enteropancreatic system of amphibians and reptiles

The diffuse chromaffin enteropancreatic system of nine species of amphibians (newts, frogs) and reptiles (turtles, lizards, snakes) was investigated immunohistochemically for the presence and topographic distribution of serotonin (5-hydroxytryptamine, 5-HT). The study revealed various numbers of serotonin-producing cells in the pancreas and intestinal epithelium and also immunolabelled nerve profiles in the villi of all species studied. In addition, two different morphological populations of serotonin cells ("open" and "closed") were localized in the functional segments of the intestines in the representative species of all the taxa investigated. Semi-quantitative evaluation of the immunolabelled pancreatic and enteric cells revealed significantly different mean numbers of labelled cells in different amphibian and reptilian taxa, and also between the various successive gut segments of each taxon. The ratio between "open" and "closed" varieties of serotonin cells recorded along the intestines followed a decreasing trend, progressive in lizards and snakes and more abrupt in newts, frogs and turtles. The above findings may help resolve several key stages of the phylogenetic evolution of poikilothermic vertebrates.