Flouxetine Improved Intravaginal Ejaculatory Latency TIME Through Decreased Levels of Interferon-gamma and Increased Levels of Serotonin in Patient with Premature Ejaculation

Pathophysiology of premature ejaculation (PE) is very complex because it is associated with many factors, which can be grouped into biological factors and psychological factors. Various diseases have been found correlate between psychological factors and biological factors through cytokines, one of which is IFN-g (IFN-g). IFN-g affect indolamine dioxygenase enzyme (IDO) and decrease levels of serotonin. Low levels of serotonin leads to PE. The purpose of this study was to prove the relationship of serotonin and IFN-g in pathophysiology of PE. This study was designed as a pretest-posttest double-blind cross-over control group design. Patients with PE were divided into 2 groups: control group and treatment group. Treatment group received flouxetine 20 mg for 30 days. Then the control and treatment groups were crossed after passing a 14-days washout period. Previously as a control group to treatment group and received flouxetine 20 mg per day for 30 days. Before and after treatment in each group was examined the levels of serotonin and IFN-g. Of the 26 subjects, each group there was 13 subjects. Flouxetine 20 mg per day for 30 days increased serotonin levels were significantly (p < 0.05), and decreased levels of IFN-g were significantly (p < 0.05). Increased levels of serotonin and decreased levels of IFN-g was significantly associated with improvements (intravaginal ejaculatory latency time) ejaculation in PE patient. From these results it can be concluded that PE occurs because decreased levels of serotonin. Decreased levels of serotonin are associated with increased levels of IFN-g

Strain-dependent variations in stress coping behavior are mediated by a 5-HT/GABA interaction within the prefrontal corticolimbic system

Background: Serotonin and γ- Aminobutyric acid (GABA) transmission is crucial in coping strategies. Methods: Here, using mice from 2 inbred strains widely exploited in behavioral neurochemistry, we investigated whether serotonin transmission in medial prefrontal cortex and GABA in basolateral amygdala determine strain-dependent liability to stress response and differences in coping. Results: C57BL/6J mice displayed greater immobility in the forced swimming test, higher serotonin outflow in medial prefrontal cortex, higher GABA outflow in basolateral amygdala induced by stress, and higher serotonin 1A receptor levels in medial prefrontal cortex accompanied by lower GABAb receptor levels in basolateral amygdala than DBA/2J mice. In assessing whether serotonin in medial prefrontal cortex determines GABA functioning in response to stress and passive coping behavior in C57BL/6J and DBA/2J mice, we observed that selective prefrontal serotonin depletion in C57BL/6J and DBA/2J reduced stress-induced GABA outflow in basolateral amygdala and immobility in the forced swimming test. Conclusions: These results show that strain-dependent prefrontal corticolimbic serotonin/GABA regulation determines the strain differences in stress-coping behavior in the forced swimming test and point to a role of a specific neuronal system in genetic susceptibility to stress that opens up new prospects for innovative therapies for stress disorders

Serotonin reuptake inhibitors and cardiovascular disease

Selective serotonin re-uptake inhibiting drugs (SSRIs) are widely used for endogenous depression. In addition to depleting the nerve terminals of serotonin they also lower blood platelet serotonin levels. Platelet aggregation is a major component of acute coronary syndromes, including sudden death, and also of limb ischaemia. Platelet-released serotonin causes constriction of diseased blood vessels. The recent literature has revealed a number of reports of association between the treatment of depression with SSRIs and reduced events caused by intra-arterial thrombosis. The effects of serotonin and serotonin depletion upon intracoronary thrombosis, diseased blood vessels, blood platelets and bleeding are discussed with recommendations for future research into the potential cardiovascular benefits of SSRIs and serotonin 5HT2A antagonists

Serotonin system implication in L-DOPA-induced dyskinesia: from animal models to clinical investigations

In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson's disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications. © 2014 Carta and Tronci

Serum Serotonin Levels Among Homosexual and Heterosexual Men

Background: Variations in sexual preferences and orientations have both proximate and ultimate causes. Serotonin (5-HT) system is a key in the regulation of reward-related behaviors, from eating, drinking to sexual activity. Recent study demonstrated that a serotonin level is involved in sexual preference in rodent as animal models. This study focuses on the profile of serotonin levels from blood among homosexual compared to heterosexual men.Methods: Eight adult (34.5±7.69) homosexual men were purposively collected from homosexual communities in Surabaya, as well thirteen adult (27.61±5.14) heterosexual men from Semarang. Complete psychological examinations were done, then serum serotonin levels were measured using ELISA. Furthermore age and Zung-self-rating depression scale were cross matched, then serum serotonin levels were tested using Mann-Whitney U Test to determine the difference of serotonin levels among two groups.Results: Our data demonstrated that 25% of homosexual men suffered from depression. There was no difference on serum serotonin levels among homosexual men compared to heterosexual men (p=0.41).Conclusion: There is no significant difference on serum serotonin levels among homosexual and to heterosexual men

Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, residente-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants

Modelling the Effect of Dorsal Raphe Serotonin Neurons on Patience for Future Rewards

Serotonin is a neurotransmitter that is implicated in many basic human functions and behaviours and is closely associated with happiness, depression and reward processing. In particular it appears to be involved in suppressing responses to distracting stimuli while waiting for a delayed reward. Here we present a system level model of the limbic system which is able to generate a serotonin (5-hydroxytryptamine [5HT]) signal so that a simulated animal waits for a delayed reward. We propose that the 5HT signal is computed by a network involving the medial Orbital Frontal Cortex (mOFC), medial Pre Frontal Cortex (mPFC), Dorsal Raphe Nucleus (DRN)and the Nucleus Accumbens Core (NAcc). The serotonin signal encodes pre-reward liking, motivation throughout the trial and delayed reward waiting. We have successfully replicated the behaviour and dynamics of laboratory studies. With the help of this model we can predict that low levels of serotonin indirectly cause less encountered rewards because the animal gives up too early

Elevated central serotonin levels inhibit emotional crying

Previous research has suggested a possible role of serotonin in emotional expressions, such as crying. We have found that a transient increase of central serotonin levels by means of oral administration of paroxetine reduces crying in response to emotional movies in healthy female volunteers. This is the first direct evidence of an important role of serotonin in this uniquely human emotional response

5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT₃ receptor resensitization due to Its subsequent release

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 μm, t(½) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 μm, t(½) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

Acute tryptophan depletion attenuates conscious appraisal of social emotional signals in healthy female volunteers

Rationale: Acute tryptophan depletion (ATD) decreases levels of central serotonin. ATD thus enables the cognitive effects of serotonin to be studied, with implications for the understanding of psychiatric conditions, including depression. Objective: To determine the role of serotonin in conscious (explicit) and unconscious/incidental processing of emotional information. Materials and methods: A randomized, double-blind, cross-over design was used with 15 healthy female participants. Subjective mood was recorded at baseline and after 4 h, when participants performed an explicit emotional face processing task, and a task eliciting unconscious processing of emotionally aversive and neutral images presented subliminally using backward masking. Results: ATD was associated with a robust reduction in plasma tryptophan at 4 h but had no effect on mood or autonomic physiology. ATD was associated with significantly lower attractiveness ratings for happy faces and attenuation of intensity/arousal ratings of angry faces. ATD also reduced overall reaction times on the unconscious perception task, but there was no interaction with emotional content of masked stimuli. ATD did not affect breakthrough perception (accuracy in identification) of masked images. Conclusions: ATD attenuates the attractiveness of positive faces and the negative intensity of threatening faces, suggesting that serotonin contributes specifically to the appraisal of the social salience of both positive and negative salient social emotional cues. We found no evidence that serotonin affects unconscious processing of negative emotional stimuli. These novel findings implicate serotonin in conscious aspects of active social and behavioural engagement and extend knowledge regarding the effects of ATD on emotional perception