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1.
The effects of hypothyroidism on 5-HT1A and 5-HT2A 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-HT1A 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-HT2A receptors in the frontal cortex in hypothyroid rats as compared with controls; this decrease was reversed by thyroxine treatment. Thus, losses of cortical 5-HT2A receptors appears to be the main consequence of hypothyroidism at the level of the serotonin system of the brain. 相似文献
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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. 相似文献
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Aim: In the present study, we assessed the role of 5‐hydroxytryptamine (5‐HT) receptors (5‐HT1A, 5‐HT2 and 5‐HT7) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia. Methods: To this end, pulmonary ventilation (VE) and body temperature (Tb) of male Wistar rats were measured in conscious rats, before and after a 0.1 μL microinjection of WAY‐100635 (5‐HT1A receptor antagonist, 3 μg 0.1μL?1, 56 mm ), ketanserin (5‐HT2 receptor antagonist, 2 μg 0.1μL?1, 36 mm ) and SB269970 (5‐HT7 receptor antagonist, 4 μg 0.1 μL?1, 103 mm ) into the NRM, followed by 60 min of severe hypoxia exposure (7% O2). Results: Intra‐NMR microinjection of vehicle (control rats) or 5‐HT antagonists did not affect VE or Tb during normoxic conditions. Exposure of rats to 7% O2 evoked a typical hypoxia‐induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY‐100635, SB269970 or ketanserin. The hypoxia‐induced hyperpnoea was not affected by SB269970 and ketanserin intra‐NMR. However, the treatment with WAY‐100635 intra‐NRM attenuated the hypoxia‐induced hyperpnoea. Conclusion: These data suggest that 5‐HT acting on 5‐HT1A receptors in the NRM increases the hypoxic ventilatory response. 相似文献
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Mikhailenko V. A. Butkevich I. P. 《Bulletin of experimental biology and medicine》2019,166(3):306-309
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... 相似文献
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慢性应激抑郁模型大鼠脑内5-HT1A和5-HT2A受体的变化 总被引:9,自引:1,他引:8
为了在5-羟色胺受体水平研究抑郁症的机制和三环类抗抑郁药物(TCAs)阿米替林的药理学机理,将24只SD雄性大鼠随机均分为三组,即对照组、抑郁组、阿米替林治疗组.应用[3H]8-OH-DPAT、[3H]Ketanserin作为标记配基,采用放射性配体受体结合法,分别测定大鼠海马5-HT1A受体、大脑皮层5-HT2A受体结合.结果显示抑郁大鼠海马 [3H]8-OH-DPAT 特异性结合(18.78±5.62 fmol/mg prot),较正常对照组(26.12±5.52fmol/mg prot )明显下降(P<0.05).抑郁大鼠大脑皮层[3H]Ketanserin特异性结合(112.58±4.21fmol/mg prot),较正常对照组(86.28±4.24fmol/mg prot)明显增加( P<0.05).阿米替林治疗3周后,可使抑郁大鼠海马5-HT1A受体与大脑皮层5-HT2A受体结合恢复正常.提示 海马5-HT1A受体结合下降、大脑皮层5-HT2A受体结合增加可能与抑郁症病因有关;海马5-HT1A受体、大脑皮层5-HT2A受体是阿米替林发挥抗抑郁作用的环节. 相似文献
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Aim and objective: The aim of the work was to characterise the nAChRs on human PBMC.
Method: PBMC were isolated from human blood buffy coats provided by the blood transfusion service and were used for radioligand binding
studies with [3H]-nicotine. RT-PCR experiments were used to determine nAChR subunit expression while immunoblotting experiments were used
to confirm that nAChR subunits identified by RT-PCR were translated into protein.
Results: Binding studies suggested the presence of one binding site for (-)- nicotine on human peripheral blood lymphocytes. Competition
studies showed that only (-)- nicotine, epibatidine and α-bungarotoxin, displaced radiolabelled nicotine from cells. RT-PCR
studies demonstrated mRNA for α4, α5, α7, β1 and β2 nAChRs subunits in PBMC. Expression of mRNA for the a5 subunit of nAChR
was observed in all lymphocyte samples tested. In contrast, the expression pattern of mRNAs for α4, α7, β1, and β2 mRNAs subunits
of nAChRs, varied between samples. Western blot analysis showed that protein for α4, α5, and α7 and β2 nAChR subunits was
expressed in most, but not all of the PBMC samples tested but some of the bands obtained were faint.
Conclusion: The results obtained suggest that human PBMC contain nAChRs containing α4β2, α4β2α5, and/or α7 subunits.
Received 6 August 2008; returned for revision 3 September 2008; received from final revision 3 October 2008; accepted by M.
Parnham 6 October 2008 相似文献
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Identification of a 5-HT1 recognition site in human brain membranes different from 5-HT1A, 5-HT1B and 5-HT1C sites 总被引:1,自引:0,他引:1
In human caudate and cortex membranes, [3H]serotonin ([3H]5-HT) labels 5-HT1A and 5-HT1C recognition sites which show nanomolar affinity for 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and mesulergine respectively, whereas no 5-HT1B binding could be identified. However, the majority of the sites labelled by [3H]5-HT (greater than or equal to 60% in cortex, 90% in caudate) are different from 5-HT1A, 5-HT1B and 5-HT1C sites. Competition experiments were performed in human caudate membranes incubated with [3H]5-HT in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine. Under those conditions, [3H]5-HT labelled an apparently homogeneous population of 5-HT1-like sites which display nanomolar affinity for tryptamines (5-carboxamido-tryptamine, (5-CT) greater than 5-HT greater than or equal to 5-methoxytryptamine (5-MeOT) greater than tryptamine) and some ergolines (metergoline greater than methysergide). In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT1A (8-OH-DPAT, buspirone), 5-HT1B (21-009, RU 24969), 5-HT1C (mesulergine, mianserin) and 5-HT2 sites (ketanserin, cinanserin). The pharmacological profile of these sites is different from that of 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2 and 5-HT3 sites but is consistent with the pharmacology of a 5-HT1-like receptor. It is very similar to that of the 5-HT1D site recently described in bovine brain by Heuring and Peroutka. 相似文献
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Past experience can alter how individuals respond to stressful events. The brain serotonin system is a key factor modulating stress-related behavior and may contribute to individual variation in coping styles. In this study we investigated whether dominant and subordinate hamsters respond differently to social defeat and whether their behavioral responses are associated with changes in 5-HT1A and 5-HT2A receptor immunoreactivity in several limbic brain regions. We paired weight-matched hamsters in daily aggressive encounters for two weeks so that they formed a stable dominance relationship. We also included controls that were exposed to an empty cage each day for two weeks. Twenty-four hours after the final pairing or empty cage exposure, subjects were socially defeated in 3, 5-min encounters with a more aggressive hamster. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains following conditioned defeat testing and performed immunohistochemistry for 5-HT1A and 5-HT2A receptors. We found that dominants showed less submissive and defensive behavior at conditioned defeat testing compared to both subordinates and controls. Additionally, both dominants and subordinates had an increased number of 5-HT1A immunopositive cells in the basolateral amygdala compared to controls. Subordinates also had more 5-HT1A immunopositive cells in the dorsal medial amygdala than did controls. Finally, dominants had fewer 5-HT1A immunopositive cells in the paraventricular nucleus of the hypothalamus compared to controls. Our results indicate that dominant social status results in a blunted conditioned defeat response and a distinct pattern of 5-HT1A receptor expression, which may contribute to resistance to conditioned defeat. 相似文献
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López-Alonso VE Mancilla-Díaz JM Rito-Domingo M González-Hernández B Escartín-Pérez RE 《Neuroscience letters》2007,416(3):285-288
The present study examined the effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence (BSS) in rats. The 5-HT1A receptor agonist, 8-OH-DPAT (0.5 microg), and the 5-HT2C receptor agonist, Ro-60-0175 (3.0 microg), were injected into the paraventricular nucleus (PVN) of rats. The animals were maintained on an ad libitum feeding paradigm with access to water and individual sources of protein, carbohydrate, and fat. Intra-PVN administration of each agonist was associated with decreased carbohydrate consumption. The effect was enhanced by the administration of both agonists together. Behavioral analysis indicated that co-administration of 8-OH-DPAT and Ro-60-0175 interrupted the natural BSS with an increase in non-feeding behavior, whereas the 8-OH-DPAT alone promoted early development of the natural BSS. In conclusion, the 5-HT receptor agonists affected serotonergic modulation of feeding behavior in a functionally selective way. 相似文献
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本研究应用免疫细胞化学技术观察了雌性成年SD大鼠下丘脑内5-HT1A受体亚型(5-HT1AR)和5-HT2AR免疫阳性结构的分布。结果显示:5-HT1AR免疫阳性神经元在视前区大细胞核、视前室周核、视上核和下丘脑外侧前核等核团内密集分布。在内侧视前核、外侧视前区、下丘脑室周核、下丘脑外侧区、背内侧核、腹内侧核、结节核、结节乳头体核、乳头体内侧核和乳头体外侧核等结构内也有较多的分布;而在正中视前核、视交叉上核、下丘脑室旁核、下丘脑背侧核、弓状核、乳头体上核和乳头体前核等部位有散在的分布。与5-HT1AR不同,5-HT2AR免疫阳性反应产物主要见于纤维和终末,阳性胞体少且染色淡。5-HT2AR阳性胞体见于下丘脑室旁核、视上核、腹内侧核、结节核、视前内侧区、外侧区、外侧前核、下丘脑背内侧核等处。另外,在视前区前内侧视前核、视交叉上核背侧和外侧可见围绕血管分布、密集成团簇状、带有大小不同膨体的阳性神经纤维缠结。本文结果提示5-HT1AR阳性结构广泛地分布于大鼠下丘脑,而5-HT2AR在下丘脑分布较为局限。二者不同的分布特点,提示它们可能介导5-HT在下丘脑的不同生理功能。 相似文献
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5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset Alzheimer's disease 总被引:1,自引:0,他引:1
Holmes C; Arranz MJ; Powell JF; Collier DA; Lovestone S 《Human molecular genetics》1998,7(9):1507-1509
The psychopathology of Alzheimer's disease (AD) is varied and includes both
behavioural and psychological symptoms. Behavioural and psychological
symptoms are common and contribute to the difficulties experienced by
carers. However, the mechanism whereby these symptoms occur in some
individuals with AD is not understood. We hypothesized that common genetic
polymorphisms in neurotransmitter systems are risk factors for these
symptoms in the course of AD. A total of 211 subjects from a
population-based prospective study of psychopathology within late-onset AD
were genotyped for the 5-HT2A receptor polymorphism 102- T/C and the 5-HT2C
receptor polymorphism Cys23Ser. Associations were found between the
presence of the C102 allele and the presence of visual (Fisher's exact
test, one-tailed, P = 0.003) and auditory hallucinations (Fisher's exact
test, one-tailed, P = 0.004) and between the presence of the Ser23 allele
and visual hallucinations (chi2 = 7.5, df = 1, P = 0.006) (P = 0.03, 0.04
and 0.06, respectively, after Bonferroni correction). In addition, there
was an association between the Cys23Ser polymorphism and hyperphagia (chi2
= 6.7, df = 2, P = 0.03) (P = 0.3 after Bonferroni correction). We conclude
that common 5- HT2A and 5-HT2C genetic polymorphisms previously showing
only weak associations with psychotic illness are associated with psychotic
symptoms in AD but are clinically silent until the onset of the
neurodegenerative process.
相似文献
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Intermale offensive aggressive behavior is facilitated by gonadal steroids and inhibited by serotonin (5-HT), presumably through its effects at 5-HT1A and 5-HT1B receptor sites. To examine the interaction between these neuroendocrine and neurochemical regulatory systems, CF-1 male mice were gonadectomized and implanted with silastic capsules containing either diethylstilbestrol (DES, a synthetic estrogen), the nonaromatizable androgens methyltrienolone (R1881) or dihydrotestosterone (DHT), or testosterone (T). Two weeks later, they were given 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist; 0.1 or 1.0 mg/kg), CGS12066B (a 5-HT1B agonist; 4.0 or 8.0 mg/kg), 0.1 or 1.0 mg/kg 8-OH-DPAT + 4.0 mg/kg CGS12066B, or vehicle, and tested for aggression. In the presence of DES, the higher 8-OH-DPAT dose given in combination with CGS attenuated aggression in comparison to vehicle controls. When given nonaromatizable androgen (R1881 or DHT), all drug treatments except 0.1 mg/kg 8-OH-DPAT significantly reduced offensive attack behavior. In the presence of T, which provides estrogenic and androgenic stimulation, aggression scores were significantly reduced when males were given the high dose of 8-OH-DPAT or CGS12066B, as well as in the 1.0 mg/kg 8-OH-DPAT + CGS12066B condition. Assessments of changes in motor behavior showed significant impairment when 8.0 mg/kg CGS12066B was administered across all hormonal conditions, indicating that reductions in offensive aggression in these treatment groups were nonspecific. The results demonstrate differential effects of the steroidal environment on the ability of 5-HT1A and 5-HT1B agonists to modulate aggression, with estrogens producing a more restrictive environment than androgens for serotonergic inhibition of male-typical aggressive behavior. 相似文献
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The lateral hypothalamus is part of an efferent system that modifies pain at the spinal cord dorsal horn, but the mechanisms by which lateral hypothalamus-induced antinociception occur are not fully understood. Previous work has shown that antinociception produced from electrical stimulation of the lateral hypothalamus is mediated in part by spinally projecting 5-hydroxytryptamine (5-HT) neurons in the ventromedial medulla. To further examine the role of the lateral hypothalamus in antinociception, the cholinergic agonist carbamylcholine chloride (125 nmol) was microinjected into the lateral hypothalamus of female Sprague-Dawley rats and nociceptive responses measured on the tail-flick and foot-withdrawal tests. Intrathecal injections of the selective 5-HT1A, 5-HT1B, 5-HT3 receptor antagonists, WAY 100135, SB-224289, and tropisetron, respectively, and the non-specific antagonist methysergide, were given. Lateral hypothalamus stimulation with carbamylcholine chloride produced significant antinociception that was blocked by WAY 100135, tropisetron, and SB-224289 on both the tail-flick and foot-withdrawal tests. Methysergide was not different from controls on the tail flick test, but increased foot-withdrawal latencies compared with controls. These results suggest that the lateral hypothalamus modifies nociception in part by activating spinally projecting serotonin neurons that act at 5-HT1A, 5-HT1B, and 5-HT3 receptors in the dorsal horn. 相似文献
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Cristiano Bombardi Giuseppe Di Giovanni 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2013,230(4):427-439
The amygdaloid complex and hippocampal region contribute to emotional activities, learning, and memory. Mounting evidence suggests a primary role for serotonin (5-HT) in the physiological basis of memory and its pathogenesis by modulating directly the activity of these two areas and their cross-talk. Indeed, both the amygdala and the hippocampus receive remarkably dense serotoninergic inputs from the dorsal and median raphe nuclei. Anatomical, behavioral and electrophysiological evidence indicates the 5-HT2A receptor as one of the principal postsynaptic targets mediating 5-HT effects. In fact, the 5-HT2A receptor is the most abundant 5-HT receptor expressed in these brain structures and is expressed on both amygdalar and hippocampal pyramidal glutamatergic neurons as well as on γ-aminobutyric acid (GABA)-containing interneurons. 5-HT2A receptors on GABAergic interneurons stimulate GABA release, and thereby have an important role in regulating network activity and neural oscillations in the amygdala and hippocampal region. This review will focus on the distribution and physiological functions of the 5-HT2A receptor in the amygdala and hippocampal region. Taken together the results discussed here suggest that 5-HT2A receptor may be a potential therapeutic target for those disorders related to hippocampal and amygdala dysfunction. 相似文献