Participation of Opioid Pathway in the Central Antinociceptive Effects of Eugenol

The aim of the present study was to evaluate the central antinociceptive effects of eugenol after intraperitoneal administration. Experiments were carried out using male Sprague-Dawley rats. Subcutaneous injection of 5% formalin-induced nociceptive behavioral responses was used as the pain model. Subcutaneous injection of 5% formalin significantly produced nociceptive responses by increasing the licking time during nociceptive behavior. Subsequent intraperitoneal injection of 100 mg/kg of eugenol led to a significant decrease in the licking time. However, low dose of eugenol (50 mg/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. Intrathecal injection of 30 µg of naloxone, an opioid receptor antagonist, significantly blocked antinociceptive effects produced by intraperitoneal injection of eugenol. Neither intrathecal injection of methysergide (30 µg), a serotonin receptor antagonist nor phentolamine (30 µg), an α-adrenergic receptor antagonist influenced antinociceptive effects of eugenol, as compared to the vehicle treatment. These results suggest that central opioid pathway participates in mediating the antinociceptive effects of eugenol.

Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.

Hop Extract Produces Antinociception by Acting on Opioid System in Mice

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 microg) or glutamate (20 microg) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an alpha2-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and alpha2-adrenergic receptors.

Antagonistas serotoninérgico e noradrenérgico por via subaracnoidea aumentam a resposta álgica em ratos / Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats

JUSTIFICATIVA E OBJETIVOS: Há evidências de que a passagem de informações nociceptivas pelo corno posterior da medula espinhal (CPME) seguindo para níveis rostrais do sistema nervoso central sofre profundas influências excitatórias e inibitórias. A presente pesquisa teve como objetivo comparar os efeitos da metissergida, da fentolamina e da fentolamina associada à metissergida, administrados por via subaracnoidea, sobre as fases I, intermediária e II do teste da formalina modificado em ratos. MÉTODO: Foram utilizados 28 ratos Wistar machos, distribuídos aleatoriamente em quatro grupos (n = 7) para receber solução salina (GC), fentolamina (GF), metissergida (GM) ou fentolamina associada à metissergida (GFM) por via subaracnoidea. A dor foi induzida pela administração de formalina na região dorsal da pata posterior direita. O teste foi dividido em três fases; fase I, intermediária e fase II. A análise estatística dos resultados foi realizada utilizando o programa SPSS (Statistical Package for Social Sciences), adotando o nível de significância de 5 por cento. RESULTADOS: Na fase intermediária, o número de elevações da pata foi significativamente maior nos grupos GF, GM e GFM quando comparados com o grupo GC. CONCLUSÕES: Os resultados sugerem a existência de efeito noradrenérgico e serotoninérgico no sistema inibitório descendente da dor aguda, com a possibilidade de emprego de agonistas serotoninérgicos e α1-adrenérgicos para controle da dor aguda.

BACKGROUND AND OBJECTIVES: There is evidence that the passage of nociceptive information through the posterior horn of the spinal cord (PHSC) on its way to rostral levels of the central nervous system undergoes profound excitatory and inhibitory influences. The objective of the present study was to compare the effects of the subarachnoid administration of methysergide, phentolamine, and phentolamine associated with methysergide on phases I, intermediate, and II of the modified phormaline test in rats. METHODS: Twenty-eight male Wistar rats distributed randomly in four groups (n = 7) to received subarachnoid saline solution (GC), phentolamine (GF), methysergide (GM), or phentolamine associated with methysergide (GFM). Pain was induced by the administration of phormaline in the dorsal region of the right hind paw. The test was divided in three phases: phase I, intermediate, and phase II. Statistical analysis of the results was performed using the software SPSS (Statistical Package for Social Sciences), adopting a level of significance of 5 percent. RESULTS: In the intermediate phase the number of paw elevations was significantly higher in GF, GM, and GFM groups when compared to the GC group. CONCLUSIONS: The results suggest the existence of a noradrenergic and serotonergic effect in the inhibitory descending system of acute pain, with the possibility of using serotonergic and α1-adrenergic antagonists to control acute pain.

JUSTIFICATIVA Y OBJETIVOS: Existen evidencias de que el paso de informaciones nociceptivas por el cuerno posterior de la médula espinal (CPME), y que continúa hacia niveles rostrales del sistema nervioso central, sufre profundas influencias excitatorias e inhibitorias. La presente investigación quiso comparar los efectos de la metisergida, de la fentolamina y de la fentolamina asociada a la metisergida, administrados por vía subaracnoidea, sobre las fases I, intermedia y II del test de la formalina modificado en ratones. MÉTODO: Fueron utilizados en el experimento, 28 ratones Wistar machos, distribuidos aleatoriamente en cuatro grupos (n = 7), para recibir una solución salina (GC), fentolamina (GF), metisergida (GM) o fentolamina asociada a la metisergida ((GFM). El dolor fue inducido por la administración de formalina en la región dorsal de la pata posterior derecha. El test fue dividido en tres fases: fase I, intermedia y fase II. El análisis estadístico de los resultados fue hecho utilizando el programa SPSS (Statistical Package for Social Sciences), [Paquete Estadístico para las Ciencias Sociales], adoptando el nivel de significancia de un 5 por ciento. RESULTADOS: En la fase intermedia, el número de elevaciones de la pata fue significativamente mayor en los grupos GF, GM y GFM cuando se comparó con el grupo GC. CONCLUSIONES: Los resultados nos sugieren la existencia de un efecto noradrenérgico y serotoninérgico en el sistema inhibitorio descendiente del dolor agudo, con la posibilidad del uso de agonistas serotoninérgicos y α1-adrenérgicos para el control del dolor agudo.

Characteristics of 5-Hydroxytryptamine Receptors Involved in Contraction of Feline Ileal Longitudinal Smooth Muscle

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the 5HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ondansetron but was inhibited by the 5-HT1 receptor antagonist methysergide and 5-HT4 receptor antagonist GR113808. These results indicate that 5-HT1 and 5-HT4 receptors may mediate the contraction of the 5-HT-induced response and 5-HT2 and 5-HT3 receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

Antinociception Effect and Mechanisms of Campanula Punctata Extract in the Mouse

In the present study, the antinociceptive profiles of Campanula punctata extract were examined in ICR mice. The Campanula punctata contain a large dose of saponin. Campanula punctata extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Campanula punctata extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microgram) was diminished by Campanula punctata extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Campanula punctata extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Campanula punctata extract in the writhing test. Our results suggest that Campanula punctata extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Campanula punctata extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.

The interaction of morphine and selective serotonin reuptake inhibitors on mechanical allodynia in rats with a spinal nerve ligation / 대한마취과학회지

BACKGROUND: Nerve injury may produce a tactile allodynia. However, there are few reports regarding the interaction of morphine and selective serotonin reuptake inhibitors (SSRIs) during a neuropathic pain state. Therefore, we investigated the antiallodynic interaction between morphine and SSRIs in a rat model of neuropathic pain. METHODS: Rats were prepared with a tight ligation of the left fifth and sixth lumbar spinal nerves and chronic intrathecal catheter implantation. Mechanical allodynia was then measured by application of von Frey filaments. Morphine, citalopram and paroxetine were administered intrathecally to obtain the dose-response curves. The 50% effective dose of morphine and citalopram or paroxetine were then coadministered to evaluate the drug interaction. In addition, naloxone and methysergide were administered to examine the reversal of the antiallodynic effect. RESULTS: Intrathecal morphine produced a dose-dependent antagonism of the tactile allodynia, but intrathecal citalopram or paroxetine showed no antiallodynic effects. In addition, a morphine-citalopram or paroxetine combination produced an increase in the withdrawal threshold, but naloxone and methysergide reversed the antiallodynic effect. In addition, no interactions were observed between naloxone and citalopram or paroxetine, or morphine and methysergide. CONCLUSIONS: These results suggest that activation of both micron-opioid and serotonin receptors is required for the increased interaction to occur between morphine and SSRIs administered to reduce tactile allodynia. Thus, serotonin receptors take part in the antiallodynic action of morphine at the spinal level.

Multiple 5-Hydroxytryptamine (5-HT) Receptors Are Involved in the Melittin-induced Nociceptive Responses in Rat I. Role of Peripheral 5-HT Receptor

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine (5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin (40microgram/paw) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635 (100microgram & 200microgram/paw), isamoltane hemifumarate (100microgram & 200microgram/paw), methysergide maleate (60microgram, 120microgram & 200microgram/paw) and ICS-205,930 (100microgram & 200microgram/paw) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.

Role of 5HT in the modification of intestinal motility, in vitro study

To determine with the mechanism of action involved in the therapeutic potential of serotonin and its blocker on gastrointestinal motility. The standard method was used for obtaining the longitudinal and circular muscles strip of rabbit ileum for in vitro studies. Each muscle strip was exposed to serotonin and its blocker and the result obtained was recorded on polygraph apparatus. The effects were recorded in vice versa fashion i.e. agonist v/s antagonist and antagonist v/s agonist on longitudinal and circular muscle strip separately. Serotonin had depressant effect on the force of contraction. On addition of antagonist in the presence of agonist, the effects were increased. Longitudinal muscle showed more pronounced effect i.e. 52.7% with methysergide in comparison to circular muscle, which was 15.6%. Circular muscle showed reduction in the force of contraction with serotonin, which was increased on addition of antagonist, but still below the level of base line contraction. Serotonin when given from external source in vitro, decreased the force, however, there was minimal increase in the rate of contraction. Hence, serotonin decreases the intestinal motility giving an impression of having antispasmodic effect. The results of this study can be utilized in the development of new drug related to G.I. motility mediated through 5HT receptors

The Mechanism of Antiallodynic Effect of Intrathecal Morphine in Neuropathic Pain Induced by Spinal Nerve Ligation: The Effect of Methysergide and Theophylline / 대한마취과학회지

BACKGROUND: Although the efficacy of morphine in a neuropathic pain state is somewhat controversial, spinally administered morphine reversed the tactile allodynia in a previous animal study. Using a behaviorial test, we examined the involvement of serotonergic and adenosine receptors in the mechanism of the antiallodynic action of the intrathecal morphine by injection of serotonergic and adenosine antagonist in a rat model of neuropathic pain induced by a spinal nerve ligation. METHODS: Male Sprague-Dawley rats were prepared with a tight ligation of the left lumbar 5th and 6th spinal nerve and a chronic lumbar intrathecal catheter implantation. Morphine 1 microgram was administered intrathecally to attenuate the tactile allodynia. Methysergide 10 microgram and 30 microgram, theophylline 20 microgram was administered intrathecally before and after the injection of morphine in order to investigate the reversal of an increased allodynic threshold by morphine. The allodynic thresholds for the left hindpaw withdrawl to von Frey hairs were assessed and converted to %MPE. RESULTS: The tactile allodynic threshold was significantly increased by 1 microgram of intrathecal morphine (P < 0.05). Methysergide 10 microgram and 30 microgram, but not theophylline 20 microgram, reversed significantly the antiallodynic effect of intrathecal morphine in pre- and post-treatment (P < 0.05). CONCLUSIONS: The results suggested that the mechanism of tactile antiallodynia induced by intrathecal morphine appears to be mediated by serotonin receptor system at the spinal level in the rat model of spinal nerve ligation.

A case of retroperitoneal fibrosis accompanying immune thrombocytopenic purpura / 대한내과학회지

Retroperitoneal fibrosis is a slowly progressing syndrome that is a part of a systemic fibrosing disease. Most causes are idiopathic, whereas the remainder are associated with methysergide ingestion, malignancy, or aneurysm of abdominal aorta. The pathogenesis is unclear, but the evidences supporting systemic autoimmune process are present, i.e. the apprearance of autoimmune antibodies, especially antinuclear antibody, positive direct or indirect Coombs' test, and the association with immune thrombocytopenia. Effective treatment with corticosteroid is another suggestion of autoimmune nature of this disease. We experienced a case of retroperitoneal fibrosis with immune thrombocytopenic purpura and positive antinuclear antibody. A 44-years old man who was in splenectomy state due to immune thrombocytopenic purpura for 15 years visited us for obstructive uropathy caused by retroperitoneal fibrosis. He was treated with double J catheter insertion in both ureters, and oral medication of corticosteroid and tamoxifen. Renal failure and thrombocytopenia was improved after treatment and the retroperitoneal fibrotic mass size decreased.

Retroperitoneal Fibrosis: Spectrum of Imaging Findings

Retroperitoneal fibrosis is a fibroproliferative process involving the retroperitoneum. It may be idiopathic or can be caused by methysergide ingestion, perianeurysmal inflammation, a leaking aneurysm, urinoma or irradiation. The symptoms and signs of retroperitoneal fibrosis are variable, and for diagnosis, imaging is therefore essential. The typical imaging finding is a fibrotic lesion in front of the lower vertebrae with ureteral obstruction. Atypical lesions, however, may occur in other parts of the retroperitoneum. The aim of this report is to describe the clinical features and various imaging findings of etroperitoneal fibrosis.

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

The antinociceptive effects of stimulating the medial (ME) and central (CE) nuclei of the amygdala in rats were evaluated by the changes in the latency for the tail withdrawal reflex to noxious heating of the skin. A 30-s period of sine-wave stimulation of the ME or CE produced a significant and short increase in the duration of tail flick latency. A 15-s period of stimulation was ineffective. Repeated stimulation of these nuclei at 48-h intervals produced progressively smaller effects. The antinociception evoked from the ME was significantly reduced by the previous systemic administration of naloxone, methysergide, atropine, phenoxybenzamine, and propranolol, but not by mecamylamine, all given at the dose of 1.0 mg/kg. Previous systemic administration of naloxone, atropine, and propranolol, but not methysergide, phenoxy-benzamine, or mecamylamine, was effective against the effects of stimulating the CE. We conclude that the antinociceptive effects of stimulating the ME involve at least opioid, serotonergic, adrenergic, and muscarinic cholinergic descending mechanisms. The effects of stimulating the CE involve at least opioid, beta-adrenergic, and muscarinic cholinergic descending mechanisms.

DEVELOPMENT OF A PAIN ASSESSMENTMODEL ANDEFFETS OF ANTIDEPRESSANTS ON NOCICEPTIVEJAWOPENING REFLEX IN FREE MOVING RATS

The purpose of the present was devalopment of a new pain assessment model that recorded in free moving rats to eliminte of anesthetic agents in orofacial area. Antinociceptive effects and mechanisms of tricyclic antidepressants is also investigated. Fifty-five male Wistar rats (400-500gm) were anesthetized with an intraperitoneal injection of urethane (500microgram/kg) and pentobarbital sodium ((20microgram/kg). Anesthetized rats mounted in a sterotaxic instrument and a guide cannula was implanted in the lateral ventricle. The Cordinates were 0.8mm posterior to bregma, 1.5mm lateral from midline and 0.4mm ventral from the skull. Stimulating electrodes implanted in the incisor plup and recording electrodes were inserted into the belly of digastric musle. Stimulating and recording eletodes were led subcutaneously to miniature cranial connector sealed on the top of the skullwhit acrylic resin. Jaw opening reflex (JOP) was used a pian assessment. Jaw opening reflex is elicted by noxious stimulation of the incisor and is quantified by the magnitude of electromyogram of digastric muscle(dEMG). After a 48hours recovery period from surgery. JOR was recorded in free moving rats. Electrcal shock (200 sec duration, 0.5-2mA intensity, 0.5Hz) were delivered to the dental plup. Twenty subsequent electromyograms were recorded from digastric music in free moving rats. After intraperitioneal injection of 15microgram/kg impramine or nortriptyline dEMG was suppressed to 64+/-6 or 56+/-8% of the control. Intraperitioneal injection of 30microgram/kg desipramine, impramine or nortriptyline dEMG respectively to 44+/-9, 15+/-4, or 16+/-3% of the control. After intravenous injection of 12microgram/kg desipramine, imipramine or nortriptyline, dEMG was suspressed to 73 7, 50 4, or 66 7% of the control. Intravenous injection of 18microgram/kg desipramine, imipramine or nortriptyline suppressed dEMG respectively to 57+/-6, 12+/-3 or 6+/-2% of the control. To investigate the central mechanisms of antinociception of nortriptyline, naloxne, opioid receptor antagonist, methysergide, and phentolamine inhibited suppression of dEMG by intravenous injection of 18microgram/kg notriptyline from 7+/-2 to 47+/-9, from 4+/-2 to 24+/-6, and from 4+/-1 to 51+/-7% of the control resectively. these results suggest that antidepressant agents be to modulate pain transmission in orofacial area. The analgesia produced by intraperitioneal and intraventous injection of antidepressants seems to be mediated by multipule pathways such as descending pain inhibitory system.

Intracisternal antidepressants suppressed the nociceptive jaw opening reflex in freely moving rats

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 musec duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of 15 microgram imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to 76+/-6% of the control. Intracisternal administration of 30 jig desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to 48 +/- 2, 27 +/- 8, or 25 +/- 5% of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from 23+/-2 to 69+/-4%, from 32+/-5 to 80+/-9%, and from 24+/-6 to 77+/-5% of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

Microinjection of glutamate into the amygdala modulates nociceptive and cardiovascular response in freely moving rats

This study was performed to examine the mean arterial pressure and nociceptive jaw opening reflex after microinjection of glutamate into the amygdala in freely moving rats, and to investigate the mechanisms of antinociceptive action of amygdala. Animals were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula (26 gauge) was implanted in the amygdala and lateral ventricle. Stimulating and recording electrodes were implanted into each of the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. After 48 hours of recovery from surgery, mean arterial pressure and digastric electromyogram (dEMG) were monitored in freely moving rats. Electrical shocks (200 musec duration, 0.5~2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minutes. After injection of 0.35 M glutamate into the amygdala, mean arterial pressure was increased by 8+/-2 mmHg and dEMG was suppressed to 71+/-5% of the control. Injection of 0.7 M glutamate elevated mean arterial pressure by 25+/-5 mmHg and suppressed dEMG to 20+/-7% of the control. The suppression of dEMG were maintained for 30 minutes. Naloxone, an opioid receptor antagonist, inhibited the suppression of dEMG elicited by amygdaloid injection of glutamate from 28+/-4 to 68+/-5% of the control. Methysergide, a serotonin receptor antagonist, also inhibited the suppression of dEMG from 33+/-5 to 79+/-4% of the control. However, phentolamine, an alpha-adrenergic receptor antagonist, did not affect the suppression of dEMG. These results suggest that the amygdala can modulate both cardiovascular and nociceptive responses and that the antinociception of amygdala seems to be attributed to an augmentation of descending inhibitory influences on nociceptive pathways via serotonergic and opioid pathways.

Effects of Methysergide on Serum Growth Hormone Response after Electroconvulsive Therapy / 대한정신약물학회지

OBJECTIVES: The purpose of this study was to investigate the effects of methysergide(serotonin receptor antagonist) on serum growth hormone response after electroconvulsive therapy(ECT). METHODS: We studied the changes of the serum growth hormone levels of the day before ECT(No ECT), ECT without methysergide pretreatment(ECT alone), and ECT with methysergide pretreatment(M+ECT) by radioimmunoassay method in 14 psychiatric patients. ECT was induced by the application of 110 volts for a period 0.3-1.0 second, using bitemporal electrodes. RESULTS: 1) Serum growth hormone levels at 15, 30, and 60 minutes after ECT were significantly increased in the ECT alone group than in the No ECT group(p<0.05). 2) Serum growth hormone levels at 15, 30, and 60 minites after ECT were significantly decreased in the M+ECT group than in the ECT alone group(p<0.05). CONCLUSION: These results suggest that the response of growth hormone after ECT seems to be mediated by the activation of serotonergic system.

Renal functional responses to a centrally-administered 5-HT-1A agonist in the anesthetized rabbits

Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT-1 (5-hydroxytryptamine-1) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT-2 and 5-HT-3 receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT-1A subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT-1A receptors. PAPP in doses ranging from 40 to 350 microgram/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption (T-cH-2O), a measure of ADH (antidiuretic hormone) secretion, was increased also. Intravenous 350 microgram/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT-2 antagonist, 40 microgram/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT-1 antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT-1A antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT-1A receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 mug/l00 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. In addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 ñ 18.55 vs 199.30 ñ 31.47 mug/mg, N = 20), and serum (l.95 ñ 0.92 vs 4.26 ñ 1.40 ng/ml, N = 20) TSH concentration (P