Inhibitory Effect Of Serotonin Research Articles

Serotonin modulates neuromuscular transmission in frogs.

The effect of 5-hydroxytryptamine (serotonin) on neuromuscular transmission in frog skeletal muscle was studied using voltage clamp technique. Serotonin produced no effect on end-plate currents during low frequency electrical stimulation of the motor nerve, but increased the amplitude depression of multiquantal currents during high-frequency stimulation similar to motor commands fired by motoneurons. It was shown that the inhibitory effect of serotonin on neuromuscular transmission is determined by slow potential-dependent block of open ionic channels in the postsynaptic membrane accumulating during rhythmic activation of the synapse.

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.

Cholinergic, noradrenergic, and serotonergic inhibition of fast synaptic transmission in spinal lumbar dorsal horn of rat

It is known that spinal nociceptive sensory transmission receives descending inhibitory and facilitatory modulation from supraspinal structures. Glutamate is the major fast excitatory transmitter between primary afferent fibers and spinal dorsal horn neurons. In whole-cell patch clamp recordings from dorsal horn neurons in spinal slices, we investigated synaptic mechanisms for inhibitory modulation at the lumbar level of the spinal cord. Application of the cholinergic receptor agonist carbachol produced a dose-dependent inhibition of glutamate-mediated excitatory postsynaptic currents (EPSCs) (IC 50 13 μM). Postsynaptic injection of two different types of G-protein inhibitors, guanosine 5′-O-2-thiophosphate or guanosine 5′-O-3-thiotriphosphate, blocked the inhibition produced by carbachol. Clonidine, a selective α-adrenergic receptor agonist, also produced a dose-dependent inhibition of EPSCs (IC 50 7 μM) that was reduced by postsynaptic inhibition of G-proteins. The inhibitory effect of serotonin was likewise mediated by postsynaptic G-proteins. Our results suggest that activation of postsynaptic neurotransmitter receptors plays a critical role in inhibition of glutamate mediated sensory responses by acetylcholine, norepinephrine, and serotonin. Our results support the hypothesis that descending sensory modulation may be mediated by multiple neurotransmitter receptors in the spinal cord.

The inhibitory effect of serotonin on the spontaneous discharge of suprachiasmatic neurons in hypothalamic slice is mediated by 5-HT 7 receptor

The effects of serotonin (5-HT) receptor agonists and antagonists on the spontaneous discharge of suprachiasmatic nucleus (SCN) neurons were investigated using rat hypothalamic slice. It was found that: (1) the SCN neurons showed a persistent rhythm in the spontaneous discharge rate, which was higher during the light phase than during the dark phase; (2) the effects of 5-HT on SCN neurons was inhibitory in nature and the sensitivity of SCN neurons to 5-HT during the light phase was lower than that during the dark phase; (3) both 5-HT and 5-HT 1/7 receptor agonist, (±)-8-hydroxy-2-(DL-N-propylamino) tetralin hydrobromide, could inhibit the spontaneous discharge of SCN neurons. This inhibitory effect could be blocked by 5-HT 2/7 receptor antagonist ritanserin and putative 5-HT 7 receptor antagonists clozapine, but neither by selective 5-HT 2 receptor antagonist ketanserin, nor by 5-HT 1 receptor antagonist pindolol. It was suggested that the inhibitory effect of 5-HT on the spontaneous discharge of SCN neurons in rat hypothalamic slice is mediated by 5-HT 7 receptor subtype.

Serotonin and Central Mechanisms Underlying Motor Control

The review considers in a historical aspect the published data on the role of serotonin in brain activity, as well as on the structure and organization of neuronal projections of serotonergic nuclei. In addition, information on the facilitatory and inhibitory effects of serotonin on neurons of various brain regions under both in vivo and in vitro conditions is presented. General characteristics of the main types of central serotonin receptors are also given. It is emphasized that such receptors form a heterogeneous group, and this is the reason for the diversity of the effects when agonists and antagonists are applied. Regularities characteristic of changes in the activity of serotonergic system over the sleep-wakefulness cycle are also analyzed in this review; data on the involvement of serotonin in motor control are cited. Possible reasons for the complexity and multiplicity of the effects evoked by serotonin at different levels of the CNS and within various neuronal structures in the course of motor behavior are discussed.

Effects of serotonin on the physiology of the rabbit small intestine

Serotonin has been shown to alter the intestinal transport of ions and intestinal motility. These effects may interfere with each other, modulating the whole physiology of the intestine. We have previously shown that serotonin also alters the transport of nutrients. Thus, the aims of the present work were to determine the possible interference between the secretagogue effect of serotonin and the mechanism by which serotonin inhibits the absorption of nutrients, and to study the effect of serotonin on the digestive activity of nutrients of the brush border membrane jejunum enterocyte in the rabbit. The results show that the secretagogue effect of serotonin neither affects the inhibitory effect of serotonin on the intestinal absorption of the nutrients, nor affects the activity of Na+/K+-ATPase. The activity of sucrase and aminopeptidase N was also not affected by serotonin in the rabbit jejunum. Finally, we also studied different parameters of the motility in the rabbit small intestine. Serotonin seemed to stimulate the motility of the rabbit small intestine by increasing integrated mechanical activity and tone of muscle fibers in duodenum, jejunum, and ileum. In conclusion, serotonin might alter or modulate the whole intestinal physiology.

Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf extract: Part V

Effect of Azadirachta indica leaf extract on serotonin inhibition in glucose mediated insulin release in rat pancreas was studied in vitro to elucidate the possible mechanism of antihyperglycemic effect of A. indica leaf extract. A. indica leaf extract blocks significantly ( P<0.05) the inhibitory effect of serotonin on insulin secretion mediated by glucose.

Inhibitory Effect of Serotonin on Feeding Behavior in Goldfish: Involvement of CRF

De Pedro, N., M. L. Pinillos, A. I. Valenciano, M. Alonso-Bedate and M. J. Delgado. Inhibitory effect of serotonin on feeding behavior in goldfish: involvement of CRF. Peptides 19(3) 505–511, 1998.—The possible action of 5-HT on feeding behavior in goldfish has been studied. Food intake was significantly reduced by intracerebroventricular (ICV) injection of serotonin (5-HT, 10 μg) at 2 h postinjection. After peripheral (intraperitoneal) administration of 5-HT (1 and 10 μg/g bw), no significant modifications in food intake were detected. Thus, it can be concluded that there is a central anoretic action of 5-HT in teleost fish. Taking in mind the inhibitory effect of corticotropin releasing factor (CRF) on feeding in teleosts and the interactions between 5-HT and CRF described in mammals, we investigated the possible involvement of CRF as mediator of the 5-HT anoretic action in goldfish. The ICV pretreatment with α-Helical CRF [9-41] (20 μg) partially blocked the inhibitory effect of 5-HT on food consumption in goldfish. These results show that CRF mediates, at least in part, the 5-HT-induced feeding inhibition in goldfish. On the other hand, the alterations in hypothalamic indoleamines content evoked by ICV treatments would suggest that the activation of CRF neurons by 5-HT appears to inhibit hypothalamic serotoninergic transmission, supporting the intermediate role of this neuropeptide in the central anoretic effect of 5-HT in goldfish.

Serotonin and Carbachol Induced Suppression of Synaptic Responses in Rat CA1 Hippocampal Area: Effects of Corticosteroid Receptor Activation In Vivo

Previous studies have shown that corticosteroids affect the changes in membrane potential evoked in CA1 hippocampal neurons by serotonin and the metabolically stable cholinergic analogue carbachol: Low corticosteroid levels induced by steroid administration to adrenalectomized rats or obtained in adrenally intact rats were associated with small transmitter responses. High corticosteroid levels induced by exogenous corticosteroid application or by an acute stress in adrenally intact rats generally evoked large transmitter responses. In the present study we investigated the consequences of this steroid modulation for the main stream of synaptic information in the CA1 hippocampal region, which is carried by amino acids. To this purpose the effect of serotonin and carbachol administration on both extracellularly and intracellularly recorded synaptic responses to Schaffer collateral stimulation were investigated. The data show that the effect of in vivo activation of corticosteroid receptors on the serotonin-induced hyperpolarization of the membrane responses is clearly reflected in the inhibitory effect of serotonin on synaptic responsiveness in the CA1 area. Low circulating levels of corticosterone or selective mineralocorticoid receptor activation reduced the serotonin mediated inhibition of synaptically evoked responses, whereas high corticosterone levels were associated with strong serotonin mediated suppression of synaptic responses. This steroid modulation seems to be specifically aimed at serotonin neurotransmission, as the cholinergic effects on excitatory synaptic transmission were not affected by the hormone treatment.

Involvement of nitric oxide and serotonin in modulation of antinociception and pressor responses evoked by stimulation in the dorsolateral region of the periaqueductal gray matter in the rat

In rats anaesthetized with alphaxalone/alphadolone, electrical stimulation in the periaqueductal gray matter in the region lying lateral and dorsolateral to the aqueduct produced a pressor response and an increase in the latency of the tail flick response to noxious heat applied to the tail. The antinociception and the pressor response were significantly attenuated following microinjection of 15 nmol 5-hydroxytryptamine at the site of stimulation in the periaqueductal gray matter. Microinjection of an equal volume of 165 mM saline had no effect. The inhibitory effects of 5-hydroxytryptamine were blocked by prior intracerebroventricular administration of 100 μg of the nitric oxide synthase inhibitor l-nitroarginine methyl ester. Neither 5-hydroxytryptamine or l-nitroarginine methyl ester had any effect on resting arterial pressure or on the baseline latency of the tail flick reflex. It is suggested that the inhibitory effects of 5-hydroxytryptamine in the dorsolateral periaqueductal gray matter are normally dependent on the functional integrity of local nitric oxide synthase-containing interneurons. Nitric oxide may act in association with 5-hydroxytryptamine to control the excitability of the aversive system in the midbrain.

P-610 - Inhibitory effect of serotonin on the induction of long-term potentiation in rat primary visual cortex

P-610 - Inhibitory effect of serotonin on the induction of long-term potentiation in rat primary visual cortex

Effect of antagonists and agonists of 5-HT1 and 5-HT2 serotonin receptors on the predator aggressiveness of wild norway rats

The effect of agonists of serotonin receptors on predator aggressiveness (the “mouse killing” test) is studied on Norway rats. Ipsapirone and eltoprazine are found to have no effect on predator aggressiveness. 1-[3-(Trifluoromethyl)phenyl]piperazine×HCl (TFMPP) considerably reduces aggressiveness. The serotonin precursor 5-hydroxyptryptophan also lowers it, while the antagonist of 5-HT2A receptors ketanserin abolishes the inhibitory effect of 5-hydroxytryptophan. Presumably, the inhibitory effects of serotonin on predator aggressiveness are realized via the 5-HT2A and 5-HT2C brain serotonin receptors.

Effects of serotonin on the release of thyrotropin-releasing hormone from the rat retina in vitro.

Effects of serotonin on the release of thyrotropin-releasing hormone (TRH) from the rat retina were studied in vitro. The retina was incubated in medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (medium) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The TRH release from the rat retina was inhibited significantly in a dose-related manner with the addition of serotonin and enhanced with cyproheptadine. The inhibitory effect of serotonin on TRH release from the retina was blocked with the addition of cyproheptadine. The elution profile of methanol extract of the rat retina was identical to that of synthetic TRH. The findings suggest that the serotonergic system inhibits TRH release from the rat retina in vitro.

P-242 - Inhibitory effect of 5-hydroxytryptamine on smooth muscle contractility of swine uterus

P-242 - Inhibitory effect of 5-hydroxytryptamine on smooth muscle contractility of swine uterus

Modulation of the activity of midbrain central gray substance neurons by calcium channel agonists and antagonists in vitro.

Changes in the background impulse activity of midbrain central gray substance neurons have been studied on slice preparations from the rat midbrain upon application of calcium-free solution, an activator of calcium channels, BAY-K 8644 (10 nM), organic (verapamil, 40 microM; D600, 10 microM; nifedipine, 1-10 microM; amiloride, 1 microM) and inorganic (Co2+, 1.5 mM) calcium channel blockers. Besides BAY-K 8644, all the substances inhibited most of the neurons studied. Verapamil, BAY-K 8644 and Co2+ also revealed facilitatory effects. Facilitatory action of BAY-K was most effective in silent neurons and in those previously inhibited by amiloride. Latent period values of inhibition in calcium-free solution and upon application of organic and inorganic blockers have the following sequence: D600 > amiloride > verapamil > Co2+ > nifedipine > calcium-free solution. Maximum rise time had the following order: amiloride > D600 > nifedipine > verapamil > Co2+ > calcium-free solution. Complete suppression of the neuronal activity induced by amiloride lasted twice as long as that induced by calcium-free solution, Co2+ and nifedipine, and six times as long as verapamil-induced suppression. Preliminary application of calcium channel blockers reduced facilitatory and increased inhibitory effects of serotonin and substance P. Data obtained are discussed with the supposition in mind that inhibition of the function of calcium channels in central gray substance neurons could be one of the mechanisms underlying the analgesic effect of a series of neurotropic agents after their introduction into this structure.

Inhibitory effect of 5-hydroxytryptamine on rat stomach fundus: mediated indirectly by activation of noradrenaline release.

Biphasic cumulative concentration-response curves to 5-hydroxytryptamine (5-HT) and alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) using rat stomach fundus in the presence of 50 microM pargyline suggested two sites of interaction (high and low affinity). The order of agonist potencies of 5-HT agonists for the high-affinity (contractile) response confirmed reports of a strong correlation of the 5-HT2B (contractile) receptor on fundus with reported rat brain (radioligand binding) pKd values at the 5-HT2C receptor (r = 0.94, b = 0.93 P < 0.01). 1(1-Naphthyl)-piperazine and ketanserin antagonized the high-affinity responses. The order of potencies for the low affinity (inhibitory) response was: alpha-Me-5-HT > 5-HT. Preincubation with mianserin or S-(-)propranolol, pretreatment with reserpine and removal of the mucosa layer resulted in amplification of the contractile effects and disappearance or reversal of the inhibitory effects of 5-HT. Activation of a second receptor site inducing catecholamine release may explain this effect of 5-HT on rat stomach fundus.

Serotonin reduces synaptic excitation of principal cells in the superficial layers of rat hippocampal-entorhinal cortex combined slices

The cells of the entorhinal cortex receive a dense innervation of serotonergic fibres from the Raphe nuclei and express a high density of 5-hydroxytryptamine 1A (5-HT 1A) receptors. We investigated the effects of serotonin on excitatory synaptic transmission in principal cells from entorhinal cortex layers II and III within hippocampal-entorhinal cortex combined slices. Although serotonin had an effect upon the membrane conductance of some, but not all cells, its most pronounced action was to reduce stimulus evoked excitatory synaptic potentials and currents (EPSP/Cs). Both α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl- d-aspartate receptor-mediated EPSPs were reduced to similar extents over a range of concentrations. Since the principal cells in layer II and layer III are the main projection cells of the entorhinal cortex, these inhibitory effects of serotonin may have implications for the transfer of information to the hippocampus.

P1-248 - Inhibitory effects of serotonin and 8-OH-DPAT on substantia nigra neurons in rat midbrain slices

P1-248 - Inhibitory effects of serotonin and 8-OH-DPAT on substantia nigra neurons in rat midbrain slices

Excitatory and inhibitory effects of serotonin on spinal axons

We studied the effects of serotonin on compound action potentials in dorsal columns isolated from young (nine to 13 days old) rats. Conducting action potentials were activated by submaximal (50%) and supramaximal constant current electrical stimuli and recorded with glass micropipettes. At 10 μM and 100 μM concentrations, serotonin significantly increased mean action potential amplitudes by9.6 ± 6.5% (± S.D., P <0.05) and16.6 ± 12.2% (± S.D., P < 0.005), respectively. Likewise, 10μM and 100μM of quipazine (a serotonhin 2A agonist) increased the amplitudes by9.6 ± 2.5% (± S.D., P < 0.0005) and37.7 ± 8.7% (± S.D., P < 0.0005), respectively. In contrast, 10 μM and 100 μM concentrations of 8-hydroxy-dipropylaminotetralin-hydrobromide (a serotonin 1A agonist) reduced axonal excitability by−9.4 ± 5.5% (±S.D., P <0.05) and−32.9 ± 10.6% (±S.D., P < 0.0005), respectively. At 50 μM concentration, mianserin (a serotonin 2A and serotonin 2C antagonist) eliminated the excitatory effects of 100 μM quipazine dimaleate. The combination of 50 μM mianserin and 100 μM serotonin reduced action potential amplitudes by−5.6 ± 4.9% (±S.D., P < 0.05). These results suggest that serotonin 1A and serotonin 2A receptor subtypes are present on spinal dorsal column axons. These two receptor subtypes have opposing effects on axonal excitability. The ratios and sensitivies of these two axonal receptor subtypes may modulate axonal excitability in rat dorsal column axons and have important implications for both development and injury of axons.

Serotonergic suppression of interhemispheric cortical synaptic potentials

The inhibitory effects of 5-hydroxytryptamine (5-HT) on interhemispheric and intracortical synaptic potentials in layer V neurons of the rat medial prefrontal (MFC) cortex were examined. Low concentrations (1–3 μM) of 5-HT selectively attenuated polysynaptic potentials that were similarly evoked by callosal or white matter stimulation. Maximally effective concentrations of 5-HT blocked interhemispheric transmission by 50–90%, as evidenced by an attenuation of the short latency callosal depolarizing synaptic potential (e-DPSP). These effects of 5-HT were not associated with a change in membrane potential or input resistance. The e-DPSP was characterized as having an N-methyl- d-aspartate (NMDA) and a non-NMDA component; the non-NMDA component was attenuated by 5-HT. Attenuation of the synaptic potential was accompanied by an attenuation of a postsynaptic glutamate potential. Suppression of both the e-DPSP and the glutamate potential was concentration dependent with 10–100 μM being maximally effective. The 5-HT 1A/2 antagonist, spiperone, antagonized the effects of 5-HT on synaptic and glutamate potentials. Spiperone (1 μM) shifted the concentration-effect curves for suppression of the e-DPSP and the glutamate potential to the right; however, the K b for the glutamate potential concentration-effect curve was 10 times that for the e-DPSP curve. The differential antagonist sensitivity of synaptic and glutamate potentials was an indication that serotonin acted on more than one receptor subtype to reduce interhemispheric transmission.