Serotonergic function and late luteal phase dysphoric disorder

Thirty-eight subjects who met criteria for the DSM-III-R diagnosis late luteal phase dysphoric disorder (LLPDD) were compared with 18 controls in 5-HT uptake kinetics of the platelets in the premenstrual (day 26) as well as in the postmenstrual phase (day 4) of the cycle. Furthermore, 5-hydroxytryptophan (5-HTP) was administered to LLPDD patients and controls in both phases of the cycle, to investigate pituitary sensitivity for serotonin. Plasma samples for the measurement of cortisol and -endorphin were taken before and after oral administration of 200 mg 5-HTP, and considered as an index of pituitary-adrenal function. LLPDD was not associated with a lower platelet 5-HT uptake and content in the premenstrual phase of the cycle, compared with the postmenstrual phase. Patients appeared not to be different from controls in 5-HT uptake kinetics of platelets in the premenstrual phase of the cycle. No main differences were observed between LLPDD patients and controls in their ability to respond with secretion of cortisol and -endorphin to 5-HTP stimulation, either in the premenstrual, or in the postmenstrual phase. This observation could not be attributed to differences in 5-HTP metabolism. The findings of the present study do not support a specific role for 5-HT in the pathophysiology LLPDD.     

MAO inhibition and the effects of centrally administered LSD,serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats

Pretreatment with the MAO-inhibitors iproniazid, clorgyline, or deprenyl abolishes the effects of LSD on the conditioned avoidance response (CAR) in rats. The effects of serotonin (5-HT) and 5-methoxytryptamine (5-MT) are greatly potentiated by these substances. Brain levels of LSD are not affected by MAO inhibition whereas levels of 5-HT and 5-MT are significantly elevated. It is postulated that the decreased behavioral response to LSD is the result of MAO inhibitor-induced changes whereas the increased response of 5-HT and 5-MT results from increased brain levels of these compounds.     

Antinociceptive action of quipazine: Relation to central serotonergic receptor stimulation

Quipazine, a serotonin receptor stimulant, inhibited the response of rats to painful stimuli in two methods currently used to measure antinociception in these animals: the hot plate and tail compression test. The antinociceptive action was observed with doses ranging from 5 to 20 mg/kg i.p. according to the test situation.The effect was significantly antagonized by a pretreatment with methergoline, a potent serotonin antagonist. An electrolytic lesion placed in the nucleus raphe medianus, which produced a marked decrease of serotonin in the forebrain did not, or only slightly, affected the effect of quipazine, depending on the method used to measure antinociception.It is suggested that quipazine can produce antinociceptive action in rats by interacting with a serotonergic mechanism. The action appears to be due mainly to a direct action on postsynaptic serotonin receptors, although a presynaptic component can also contribute to the effect of quipazine.Visiting scientist from Clinica Neurologica, UniversitàVisiting scientist from Clinica Neurologica, Università     

Molecular serotonergic mechanisms appear to mediate genetic sensitivity to cocaine-induced convulsions

Cocaine-induced convulsions appear to be mediated by serotonin (5-HT) neurotransmission, acting primarily at 5-HT(2) receptors. However, this effect of cocaine is attenuated by cocaine binding at sigma and muscarinic M(1) and M(2) sites. This study examined whether the aforementioned neural sites mediate the nearly two-fold difference in sensitivity to cocaine-induced convulsions across C57BL/6J (6J) and C57BL/6ByJ (6ByJ) mice. Experiment 1 compared 5-HT transporter densities across several brain regions of 6J and 6ByJ mice and cocaine-induced convulsions following pretreatment with the 5-HT reuptake inhibitor fluoxetine. Experiment 2 compared 5-HT(2) receptor densities across these mice and cocaine-induced convulsions following pretreatment with the 5-HT(2) antagonist cinanserin. There were no differences in 5-HT transporter densities, however, fluoxetine produced a greater facilitation of cocaine-induced convulsions in 6ByJ relative to 6J mice, suggesting that sensitivity to convulsions is mediated postsynaptically. Indeed, 5-HT(2) density was higher in 6ByJ relative to 6J mice in the amygdaloid ridge, hypothalamus, and midbrain. In addition, cinanserin attenuated convulsions more potently in 6J relative to 6ByJ mice. There were no differences in the densities or affinities of 5-HT(1), muscarinic, or sigma receptors across these strains, suggesting that density of these latter sites does not mediate genetic sensitivity to cocaine-induced convulsions. Since 6ByJ mice are less sensitive to convulsions despite the fact that they have more 5-HT(2) receptors, we hypothesized that these mice may exhibit a weaker linkage of 5-HT(2) sites to their second-messenger system relative to 6J mice. However, in experiment 3 we demonstrated that 5-HT(2)-receptor mediated phosphoinositide hydrolysis was higher in 6ByJ relative to 6J mice in the same regions also displaying higher 5-HT(2) densities. This study suggests that 5-HT(2) receptors mediate genetic sensitivity to cocaine-induced convulsions, further supporting the role of these sites in mediating this toxic effect of cocaine.     

Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion

Background: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.Methods: TS mice mod...     

脑内五羟色胺与干扰素镇痛

由侧脑室或在中脑导水管周围灰质内微量注射入白细胞α-干扰素可以引起大鼠痛阈明显上升,但脑内5-HT和5-HIAA均无变化。看来干扰素的镇痛作用和脑内5-HT递质无关,它可能是不经过5-HT的释放也不和吗啡受体结合起作用的另一类型的镇痛物质。     

家兔消化道5-羟色胺免疫活性细胞的免疫组织化学研究

目的 通过免疫组织化学染色了解5-羟色胺(5-HT)免疫活性阳性细胞在家兔消化道内的分布位置及其形态。方法 取家兔消化道,冲洗、固定、石蜡切片,用ABC(avidin-biotin-peroxidase complex)免疫组织化学法检测5-HT阳性细胞。结果 食管和胃贲门部呈阴性反应,其他部位均有5-HT细胞分布,分布的密度近似呈字母“M”形。5-HT细胞形态以圆形或椭圆形为主,只有小肠段5-HT细胞呈梭形具有突起,直肠部5-HT细胞呈锥体形。5-HT细胞多分布于粘膜上皮或腺泡上,但直肠部的5-HT细胞位于固有膜内。结论 家兔的食性、消化特点对5-HT细胞分布型形成有一定影响,5-HT细胞形态与其内、外分泌功能是相适应的。     

Serum Leptin Levels in Patients with Premature Ejaculation

Leptin is a fat cell-derived hormone signaling the hypothalamus about food intake, the regulation of weight, and sexual behavior. The inhibitory effect of serotonin on libido, ejaculation, and orgasm is well documented. There is an interaction between leptinergic and serotonergic systems in the central nervous system. This study was conducted to evaluate serum leptin levels of the patients with premature ejaculation. The study group consisted of 15 patients with premature ejaculation according to Diagnostic and Statistical Manual of Mental Disorders, Third Revised Version ( DSM -III-R) and 15 healthy controls. The fasting serum leptin levels were measured. Significantly high serum leptin levels in the patients were found after body mass index or age adjustment. The intravaginal ejaculation latency time negatively correlated with leptin levels in both patient and control groups. In addition, there was a positive correlation between leptin levels and the duration of illness. It would appear that leptin may be associated with premature ejaculation.     

Dorsal raphe nucleus stimulation modulates the response of layers IV and V barrel cortical neurons in rat

The effect of dorsal raphe nucleus (DRN) electrical stimulation on response properties of layers IV and V barrel cortical neurons was studied. To assess the receptive field characteristics of cortical neurons, responses of neurons were recorded following the displacement of principal and adjacent whiskers individually or in a condition test paradigm. Then neuronal responses to the displacement of whiskers were analyzed following DRN stimulation at 0, 50, 100, 200 and 400 ms inter-stimulation intervals. Considering On responses, DRN stimulation suppressed the response magnitude of layer V neurons to principal whisker deflection, while it slightly increased that of layer IV neurons (not statistically significant). The response latency of layer IV neurons increased when DRN was stimulated 200 or 400 ms before principal whisker deflection, while the response latency of layer V was not changed. DRN stimulation had no effect on either magnitude or latency of neuronal response to the adjacent whisker deflections. We observed a decrease in the inhibitory effect of the adjacent whisker deflection on the magnitude of neuronal response to the principal whisker deflection in layer IV when DRN was stimulated 200 ms before the principal whisker deflection. Off responses did not show any significant effect of DRN stimulation. Our results suggest a modulating role for DRN in processing of the incoming information into barrel cortex. This effect might be location dependent.     

CSF monoamine patterns in pathological gamblers and healthy controls

Previous reports on compounds in the cerebrospinal fluid (CSF) of pathological gamblers have focused on disturbed NA, DA and 5-HT function in the central nervous system. We have analysed precursors, transmitters and transmitter metabolites in 3 x 6 ml of CSF obtained from one female and 11 male pathological gamblers and 11 healthy male controls lumbar punctured at the L4-5 level after 8 h of fasting without preceding strict bedrest. Pathological gamblers displayed lower CSF levels of tryptophan and 5-HT while the opposite was the case for 5-HIAA, tyrosine, DA, HVA, DOPAC and HMPG. In contrast to previous studies, the NA level did not differ between pathological gamblers and healthy controls. A disrupted CSF gradient was noted for tryptophan, 5-HT, DA, HVA, DOPAC, NA and HMPG, but only in pathological gamblers. A disrupted gradient was found for 5-HIAA in both pathological gamblers and healthy controls. The results are in line with the presence of altered indoleamine and catecholamine function in pathological gamblers as well as an altered CSF transport from the brain to the lumbar compartment in such gamblers.