There is much evidence indicating that the serotonergic system involves in the central regulation of nociceptive sensitivity. However, the exact mechanism of serotonergic system and also its interaction with other neural systems has not yet been understood. In this study, the effect of serotonin (5-HT) and fenfluramine, as a serotonin releaser, on formalin induced pain and also its possible interaction with opioidergic system have been studied. Results obtained from this study show that serotonin in intrathecal (100 mg/rat, i.t.) and intracerebroventricular (100 mg/rat, i.c.v.) administration produces significant (P < 0.05) analgesia in early and late phase offormalin test. These analgesic effects were abolished by pretreatment with the naloxone hydrochloride (2 mg/kg, Lp.). Furthennore, fenfluramine (10 mg/kg, i.p.) induced analgesia in both phases which has been reversed by pretreatment with the naloxone (2 mg/kg, i.p.). The results of our study may indicate that serotonin induces antinociceptive effect in chronic inflammatory pain through activation of opioidergic neurons, but it needs more investigation in order to clarify the mechanism of this interaction.

Introduction. About 50% of serotonergic neurons of the C.N.S exist in the dorsal raphe nucleus. To change the serotonin's rate of C.N.S induces many disorders. Due to age increase, morphologic changes in number and diameter of dendrites, number of their spines, number of fibers and cellular endings in the nucleus raphe dorsalis and rate of their staining are observed. The aim of this research is to survey of any changes in neurons numbers and volume of nucleus raphe dorsalis in aging.Materials and Methods. In this research 15 female albino rats with age of 3 days, 2 and 12 months were used. The brain of these rats fixed by perfusion method with BOEIN solution, then the specimens stained by Cluver and Barrera method. The number of cells and volume of the nucleus raphe dorsalis have been calculated by using eye peace microscope. The data were analysed by Kraskul-Wallis test and P< 0.05 was considered as significant.Results. Microscopic examinations have been shown that with increasing age the number of neurons of the nucleus raphe dorsalis and the volume of them significantly decreased (P<0.05).Conclusion. These quantitative  changes in higher ages, make the negative effects in vital activity of the neurons, which may induce many disorders.

Sertraline is selective serotonin reuptake inhibitor (SSRI) that is commonly used in adults in the treatment of mood and anxiety disorders, but it is not currently approved for the use in pediatric patients. Considering controversial reports about safety and efficacy of sertraline in childern, it is necessary to review the recent studies and case reports regarding the therapeutic effects, dosage, side effects and overdose of sertraline in children and adolescents. Some studies showed that sertraline may be particularly useful for management of young patients with major depressive disorder and QCD. The safety of sertraline is superior to Tricyclic Antidepressants (TCAS).      

In order to understand the function of mammalians serotonin system, we have to know the anatomical structure, because physiological changes are influenced through the anatomical changes. A number of thalamic nuclei are associated with functions known to influenced by serotonergic input in brainstem, among them mediodorsal thalamic uncleus has relationship with limbic system and prefrontal cortex.The precise topographical projections of mesencephalic raphe nuclei to the MDnucleus of thalamus were identified in the rat using Horseradish peroxidase (HRP) retrograde tracing substance. Injection of HRP in MD labeled a large number of neurons in rostral to caudal part of dorsal raphe nucleus. It exhibited a strong number of neurons in ipsilateral part of DR and a few cells in its contralateral part. Numerously labeled cells were also observed ipsilateral in rostral and medial part of MnR (86%) and a few cells in it’s contralateral part. The present study has provided that the MD innervation by DR is more greater in density than that observed at the MnR. Upon these results and previous study, mesencephalic raphe nuclei are involved in several specific functions of thalamus as limbic system behavioral mechanism.A much more detailed knowledge is needed to show topographic relationships between mesencephalic raphe nuclei and forebrain.

Autism and the other disorders in the autism spectrum are behaviorally defined syndromes that can be a prolonged disorder. The specific underlying neurophysiological mechanisms simply not known, but probably several causes lead to disorders in the autism spectrum. This article is summary of recent research about etiology of autism but the search must continue. 1) Neurobiological origin, the neurobiological investigations show the role of dopamine and serotonin in pathogenesis of autism. 2) Genetic, studies in autism was established the hypothesis that genetic factors can be etiologically significant in subsets of patients. 3) With the Regional cerebral glucose metabolism measurement, autistic children had a left > right anterior rectal gyrus asymmetry as opposed to the normal right> left asymmetry in that region. 4) With the Regional cerebral blood flow measurement; no cortical regional abnormalities were found. 5) Association of epilepsy and autism; pediatric epilepsy lead to autistic regression. 6) Association of tuberous sclerosis and autism; the number of tubers was significantly greater in individuals with a diagnosis of autism those without this diagnosis. 7) Embryological origin for autism, the results and two new lines of evidence that place the initiating injury for autism around the time of neural tube closure. 8) Obstetric complications and later autistic disorder, these data do not support the view that obstetric complications increase the risk for later autism. 9) Food allergy, recent findings show a relationship between food allergy and infantile autism. 10) Head circumferences measurement, in children with autism show the larged head circumferences and increased growth.  

There is marked elevation of endogenous opioid levels in plasma of human subjects with biliary cirrhosis as well as animal model of cholestasis. In addition, development of morphine tolerance and dependence has been shown to be inhibited by drugs which reduce brain serotonin levels. However, i.c.v. injection of serotonin increases the morphine analgesia. In the persent study we have investigated the role of serotonergic pathway in determining the withdrawal syndrome in mice model of cholestasis. There were three experimental groups: unoperated mice, sham operated mice and mice in which the main bile duct was ligated. Physical dependency was assessed by precipitating a withdrawal syndrome by naloxone (2 mg/kg) five days after induction of cholestasis. Acute and chronic administration of serotonin receptor antagonists, cyproheptadine (5 mg/kg), methysergide (3 mg/kg) and tropisetrone (10 mg/kg) attenuated withdrawal and decreased the antinociception. However, acute treatment by fluoxetine (15 mg/kg), an inhibitor of serotonin uptake, increased the withdrawal signs and antinociception, and chronic administration of fluoxetine during five days after induction of cholestasis decreased the naloxone precipitated withdrawal syndrome and antinociception. These experiments lead us to conclude that the naloxone-precipitated withdrawal signs which occur in mouse model of cholestasis, are potentially dependent on serotonergic pathway.

History and Objectives:Fluoxetine is an anti-depressant drug that specifically inhibits serotonin re-uptake. Since fluoxetine can lead to bradycardia and may have pro-arrhythmic and antiarrhythmic properties, this study was carried out to evaluate the effect of fluoxetine on ouabain-induced arrhythmia in isolated atrium of Guinea pig.Materials and Methods:In this study, Guinea pigs from both sexes (350-600 g) were used. The animal's atrium was totally isolated from the ventricle. Thirty-two isolated atria were studied in 4 groups, that is, control, fluoxetine, ouabain, and ouabain in combination with fluoxetine. The isolated atria were inserted into modified oxygenated Krebs solution. Thereafter, the mentioned drugs were added to the bath and 20 min later, ionic content of the tissue was measured.Results:Fluoxetine (2-16 mg) can produce a short increase in contractile force (4 min), but finally decrease force and rate of isolated atrium. Ouabain (1.2 mg/ml) can lead to atrial arrhythmia after 1.5 min and after 16 min leads to total toxicity, asystole, and atrial cease. Fluoxetine pretreatment (4 mg/ml) can delay the occurrence of arrhythmia up to 5 min (P<0.05). Meanwhile, survival time for atrium increased to greater than 40 min (P<0.05). Ionic measurement of atrial tissue showed that ouabain by itself can increase the level of sodium, but no such effect on potassium and calcium levels. In addition, fluoxetine in itself can significantly increase potassium level (P<0.05). Administration of fluoxetine and thereafter, ouabain can attenuate the toxic effect of ouabain on ionic changes and even return it to normal level.Conclusion and Recommendations:It is concluded that fluoxetine has a direct negative inotropic and chronotropic effect on isolated atrium as a possible result of inhibition of sodium and calcium channels, and it can probably prevent ouabain-induced toxicity and arrhythmia in atrium of Guinea pig through stabilization of cell membrane and/or prevention of ionic changes that is a quinidine-like effect.