Intravenous Serotonin Research Articles

Comparison of Ramosetron, Ondansetron, and Granisetron in Attenuating Maternal Hypotension after Spinal Anesthesia in Patients Undergoing Lower Segment Caesarean Section

Abstract Background: Spinal anesthesia (SA) has many advantages in lower segment caesarean section (LSCS), but hypotension is the main issue that can be managed in different ways. This study was conducted to know the effectiveness of three intravenous serotonin receptor antagonists (ramosetron, ondansetron, and granisetron) in the prevention of bradycardia and hypotension during LSCS under SA. Patients and Methods: A total of 160 parturients posted for LSCS under SA were enrolled in this study and divided equally into four groups. Five minutes before SA, Group R received intravenous (IV) 0.3 mg ramosetron, Group O received 4 mg ondansetron IV, Group G received 1 mg granisetron IV, and Group S received IV normal saline. All solutions were diluted with normal saline to 5 mL to blind the drugs. Heart rate (HR), systolic and diastolic blood pressure, and mean arterial pressure were recorded. The total consumption of vasopressor and side effects were recorded. Results: The decrease in mean arterial pressure and mean HR was significantly lower in group R than other groups at all intervals (P < 0.05). The incidence of hypotension was 25% in group R compared with 42.5%, 55%, and 72.5% in groups O, G, and S, respectively. Conclusion: Premedication with intravenous ramosetron significantly reduced hypotension, HR, and total vasopressor usage in LSCS parturients. Intravenous ondansetron and granisetron had lesser effects than ramosetron.

Seroprevalence of leptospirosis among people in Shabramant Village, Egypt

Background Spinal anesthesia avoids the hazards of airway management during general anesthesia. Shivering is a frequent risk factor in patients undergoing lower half operations under spinal anesthesia. Premedication with intravenous serotonin receptor antagonists such as granisetron has been used to overcome this problem. Ketamine increases arterial pressure and heart rate and may decrease core-to-peripheral redistribution of heat. Moreover, pethidine which is considered as a time-tested drug for control of shivering can be of value for shivering prophylaxis. Objective This study evaluates the efficacy of granisetron, ketamine, and pethidine on shivering in patients undergoing lower half operation under spinal anesthesia. Patients and methods A total of 60 patients were assigned to three equal groups: group G received 3 mg granisetron, group K received 25 mg ketamine, and group P received 25 mg pethidine 5 min before spinal anesthesia. The incidence of shivering episodes was recorded at baseline monitoring, intraoperatively, and postoperatively. Moreover, propagation and regression of motor and sensory block were assessed. Results Regarding mean arterial blood pressure, there was significant decrease in group P in comparison with groups G and K. Regarding decreased incidence of shivering, there was no significant difference between the study groups. Regarding incidence of nausea and vomiting, there was significant decrease incidence in group G compared with groups K and P. Moreover, there was significant difference regarding faster time to regression of sensory block in group G in comparison with groups K and P. Conclusion In patients undergoing lower half surgery under spinal anesthesia, prophylactic intravenous administration of 3 mg granisetron, 25 mg ketamine, or 25 mg pethidine 5 min before induction of spinal anesthesia significantly reduced the severity of shivering. Regression of sensory block was faster with granisetron than ketamine and pethidine. Moreover, prophylactic granisetron also reduces nausea and vomiting and the need of antiemetics.

The Effect of Intravenous Citalopram on the Neural Substrates of Obsessive-Compulsive Disorder.

This study investigated the effect of an intravenous serotonin reuptake inhibitor on the neural substrates of obsessive-compulsive disorder (OCD), as intravenous agents may be more effective in treating OCD than conventional oral pharmacotherapy. Eight OCD subjects and eight control subjects received alternate infusions of citalopram and placebo during functional magnetic resonance imaging, in a randomized, symptom-provocation, crossover design. Compared with baseline, OCD subjects displayed significant changes in prefrontal neural activity after the citalopram infusion relative to placebo, and these changes correlated with reductions in subjective anxiety.

Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs.

To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.

Calmodulin inhibitors suppress calcium signaling from serotonin receptors in smooth muscle cells and abolish vasoconstrictive response on intravenous introduction of serotonin

Comparative study of the effect of calmodulin inhibitors (trifluoperazine, W-12, and W-13) and the TRPVI channel blocker (capsazepine) on receptor-dependent calcium exchange in smooth muscle cells of the rat aorta and on the contractility of the isolated aorta was conducted. It was determined that trifluoperazine almost completely removes an increase in the concentration of calcium ions in the cytoplasm of smooth muscle cells (isolated from the rat aorta) and smooth muscle cells of the A7r5 line in response to serotonin and does not influence the cell response to vasopressin and angiotensin II. W-12 and W-13 also do not reduce calcium ion concentration increase (induced by vasopressin and angiotensin II) but reduces by two times its rise in response to serotonin. It was found that the efficiency of calcium exchange suppression by calmodulin inhibitors correlates with the intensity at which they inhibit the contractile response of the aorta on the effect of serotonin. It was detected that the inhibiting effect of calmodulin blockers on calcium exchange in smooth muscle cells and the contractility of the rat isolated aorta during the activation of serotonin vasoconstrictive receptors are realized by a TRPV1-independent mechanism. It was demonstrated in experiments in vivo that trifluoperazine does not influence hypotensive reaction in rats (normally observed in response to intravenous serotonin introduction), but removes the hypertensive effect of this neurotransmitter in rats after chronic introduction of dexamethasone. The results obtained confirm the hypothesis (that we previously stated) about the direct involvement of calmodulin in signal transmission from vasoconstrictive serotonin receptors.

Local antagonism of intertrigeminal region metabotropic glutamate receptors exacerbates apneic responses to intravenous serotonin.

Injections of a broad spectrum glutamate receptor antagonist into the pontine intertrigeminal region (ITR) exacerbate vagal reflex apnea produced by intravenous serotonin infusion. This effect is not reproduced by ITR injections with either NMDA or AMPA receptor antagonists. Here, we tested the hypothesis that ITR injection with a metabotropic glutamate antagonist would alter respiratory responses to serotonin (5-HT) intravenous infusions. In anesthetized adult male rats (N=20; Sprague-Dawley) AIDA (1-aminoindan-1,5-dicarboxylic acid), a specific antagonist of the type 1 metabotropic glutamate receptor (mGlu1R), was microinjected unilaterally into the ITR to block 5-HT evoked apnea. Respiratory pattern changes evoked by ITR-glutamate injection and by intravenous serotonin (5-HT) infusion (0.5 microl, 0.05 M; or 2.5x10(-8) mol) were characterized according to apnea expression and duration, as well as coefficients of variation for breath duration (CVTT) and amplitude (CVVT) before and after ITR AIDA injection. Unilateral AIDA blockade of the ITR significantly increased the duration of apnea evoked by 5-HT infusion (p<0.03 for each dose tested) during the 30s following infusion in a dose-dependent fashion, with the two highest doses resulting in intermittent apneas for at least 10 min following a bolus 5-HT infusion. Similar prolonged increases in CVTT and CVVT with respect to control were associated with ITR AIDA injections. These findings suggest that brief perturbations of vagal afferent pathways can produce ongoing respiratory dysrhythmia, including spontaneous apnea, and that glutamatergic neurotransmission within ITR may be important for damping such disturbances. The present observations also suggest that such respiratory damping may be mediated by mGlu1 receptors. These findings extend our understanding of the role of the intertrigeminal region in modulating respiratory reflexes.

Effect of serotonin on small intestinal contractility in healthy volunteers

The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase III frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile activity. Platelet-depleted-plasma levels of serotonin increased 2-fold following both intravenous and high doses of intraluminal infusions of serotonin. All subjects reported minor short-lived adverse effects following intravenous serotonin stimulation, while only half of the subjects reported minor short-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers.

Effect of serotonin on respiration, cerebral circulation, and blood pressure in rats

The effects of intravenous serotonin on respiration, cerebral circulation, and blood pressure were examined in narcotized rats. Serotonin rapidly decreased local cerebral blood flow (by almost 30%) and blood pressure. Hemodynamic phenomena were accompanied by sharp changes in the respiration pattern: short-term apnea in all cases. The mechanism of this apnea was related to initial stages in blood pressure changes and had a neurogenic nature.

Supranodose Vagotomy Precludes Reflex Respiratory Responses to Serotonin in Cats

Mediation of the respiratory reflex effects of an exogenous serotonin challenge goes beyond the lung vagi and is suggested to involve the nodose ganglia. In the present experiments the effects of an intravenous serotonin challenge on breathing pattern were studied in 8 pentobarbitone-chloralose anaesthetised cats. Bolus injection of serotonin oxalate (50 µg/kg) into the right femoral vein evoked prompt apnoea of 19.2 (± 2.4)-second duration in all 8 cats while intact; the apnoea was much shorter after midcervical vagal section (8.1 ± 0.9 s, p < 0.001), and was abolished by supranodose vagotomy. In post-apnoeic breaths, the tidal volume was reduced from a baseline of 34.1 ± 4.0 to 13.5 ± 1.1 ml (p < 0.001) prior to, and from a baseline of 43.9 ± 5.4 to 33.8 ± 6.6 ml (p < 0.01) after midcervical vagotomy; the serotonin challenge did not affect tidal volume following supranodose vagal section (p = 0.4). The increase in respiratory rate found in intact (p < 0.001) and midcervically vagotomised cats (p < 0.01) was eliminated by the neurotomy above the nodose ganglia. Supranodose vagotomy altered cardiovascular response to serotonin by replacing the fall in blood pressure with an increase. These data suggest that the sequelae of serotonin-induced pulmonary chemoreflex, i.e. respiratory arrest, cardiovascular changes and post-apnoeic pattern of breathing require intact nodose ganglia.

Supranodose vagotomy precludes reflex respiratory responses to serotonin in cats

Mediation of the respiratory reflex effects of an exogenous serotonin challenge goes beyond the lung vagi and is suggested to involve the nodose ganglia. In the present experiments the effects of an intravenous serotonin challenge on breathing pattern were studied in 8 pentobarbitone-chloralose anaesthetised cats. Bolus injection of serotonin oxalate (50 microg/kg) into the right femoral vein evoked prompt apnoea of 19.2 (+/- 2.4)-second duration in all 8 cats while intact; the apnoea was much shorter after midcervical vagal section (8.1 +/- 0.9 s, p < 0.001), and was abolished by supranodose vagotomy. In post-apnoeic breaths, the tidal volume was reduced from a baseline of 34.1 +/- 4.0 to 13.5 +/- 1.1 ml (p < 0.001) prior to, and from a baseline of 43.9 +/- 5.4 to 33.8 +/- 6.6 ml (p < 0.01) after midcervical vagotomy; the serotonin challenge did not affect tidal volume following supranodose vagal section (p = 0.4). The increase in respiratory rate found in intact (p < 0.001) and midcervically vagotomised cats (p < 0.01) was eliminated by the neurotomy above the nodose ganglia. Supranodose vagotomy altered cardiovascular response to serotonin by replacing the fall in blood pressure with an increase. These data suggest that the sequelae of serotonin-induced pulmonary chemoreflex, i.e. respiratory arrest, cardiovascular changes and post-apnoeic pattern of breathing require intact nodose ganglia.

Cardiovascular responses elicited during binge administration of cocaine

Cocaine use is often characterized by a repeated pattern of frequent administrations (binge) followed by periods of abstinence. The repeated binge administration of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) alters cardiovascular function and the arterial pressure and heart rate responses elicited by these drugs. Whether repeated binges of cocaine similarly affect cardiovascular function and cardiovascular responsiveness is unknown. Radiotelemetry was used to record the cardiovascular responses elicited during three successive cocaine binges (5 mg/kg, t.i.d., for 4 days) in conscious, unrestrained rats. Each binge was separated by a 10-day cocaine-free period. The effects of cocaine administration on vascular reactivity and vasovagal, Bezold–Jarisch reflex function were also evaluated. The intravenous administration of cocaine increased both mean arterial pressure (MAP) and heart rate. The arterial pressure and heart rate responses elicited by cocaine, both within and between the binges, were remarkably similar. The arterial pressure and heart rate responses elicited by the intravenous administration of sodium nitroprusside, acetylcholine and phenylephrine before each binge and 10 days after the last binge were not altered after the binge administration of cocaine. Likewise, Bezold–Jarisch reflex function elicited by intravenous serotonin was unchanged after the binge administration of cocaine. These results indicate that the administration of cocaine using this repeated binge model does not alter the arterial pressure and heart rate responses elicited by the drug, nor does it alter the cardiovascular responses elicited by a variety of vasoactive substances.

Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging.

We examined the sequence of neural responses to the hypotension, bradycardia, and apnea evoked by intravenous administration of 5-hydroxytryptamine (serotonin). Functional magnetic resonance imaging signal changes were assessed in nine isoflurane-anesthetized cats during baseline and after a bolus intravenous low dose (10 microg/kg) or high dose (20-30 microg/kg) of 5-hydroxytryptamine. In all cats, high-dose challenges elicited rapid-onset, transient signal declines in the intermediate portion of the solitary tract nucleus, caudal midline and caudal and rostral ventrolateral medulla, and fastigial nucleus of the cerebellum. Slightly delayed phasic declines appeared in the dentate and interpositus nuclei and dorsolateral pons. Late-developing responses also emerged in the solitary tract nucleus, parapyramidal region, periaqueductal gray, spinal trigeminal nucleus, inferior olivary nucleus, cerebellar vermis, and fastigial nucleus. Amygdala and hypothalamic sites showed delayed and prolonged signal increases. Intravenous serotonin infusion recruits cerebellar, amygdala, and hypothalamic sites in addition to classic brain stem cardiopulmonary areas and exhibits site-specific temporal patterns.

ANP, BNP, and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep.

We demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia to intravenous serotonin [5-hydroxytryptamine (5-HT)] (von Bezold-Jarisch reflex) in rats. To determine whether 1) ANP affects this cardiopulmonary vagal reflex in another species and 2) B-type (BNP) and C-type (CNP) natriuretic peptides share with ANP the ability to modulate this reflex, we used intravenous phenylbiguanide (PBG), a 5-HT(3) agonist, as the stimulus to evoke a von Bezold-Jarisch reflex (dose-related, reproducible bradycardia) in conscious adult sheep (n = 5). Three doses of PBG (13 +/- 3, 20 +/- 3, and 31 +/- 4 microg/kg) injected into the jugular vein caused reflex cardiac slowing of -7 +/- 1, -15 +/- 2, and -36 +/- 3 beats/min, respectively, under control conditions. These doses of PBG were repeated during infusions of ANP, BNP, or CNP (10 pmol. kg(-1). min(-1) iv), or vehicle (normal saline). Each of the natriuretic peptides significantly (P < 0.05) enhanced the sensitivity of bradycardic responses to PBG by 94 +/- 8% (ANP), 142 +/- 55% (BNP), and 61 +/- 16% (CNP). Thus not only did ANP sensitize cardiopulmonary chemoreceptor activation in a species with resting heart rate close to that in humans, but BNP and CNP also enhanced von Bezold-Jarisch reflex activity in conscious sheep.

Effects of vagal and laryngeal afferents on apnoeic response to serotonin in cats

Intravenous serotonin (5-HT) elicits apnoea followed by subsequent, shallow tachypnoea. The present study was designed to ascertain whether laryngeal afferents play a role in the respiratory reflex response. Administration of 5-HT into the femoral vein (i.v.) or to the laryngeal artery (lar. art.) in anaesthetized, spontanously breathing cats caused an expiratory apnoea that was significantly reduced (i.v.) or abolished (lar. art.) by bilateral midcervical vagotomy. Subsequent bilateral division of the superior laryngeal nerves (SLNs) did not affect the magnitude of apnoea on i.v. administration. Supranodose vagotomy abolished the occurrence of post-serotonin apnoea following i.v. injection, which is consistent with earlier results. During the phase of rapid, shallow breathing the peak respiratory airflows were significantly increased on i.v. 5-HT injection in all neural states of cats, whereas laryngeal artery administration failed to produce a significant change in respiratory airflows from baseline. Serotonin significantly increased breathing frequency in the intact and denervated (vagus and SLN cut bilaterally) cats independent of the route of injection. The results show that serotonin affects the respiratory pattern with large contribution of pulmonary vagal but not laryngeal afferents. However, the occurrence of the expiratory apnoea was related to large extent to the integrity of the infranodose vagi.

Physiologic Significance of Epithelial Removal on Guinea Pig Tracheal Smooth Muscle Response to Acetylcholine and Serotonin

We studied the modulatory effect of airway epithelium on guinea pig tracheal smooth muscle (TSM) contraction. Isometric force was measured in vivo before and after removal of the tracheal epithelium. In parallel studies, TSM contraction was also measured isometrically in epithelium-intact and epithelium-denuded TSM strips in vitro. Epithelial removal in vivo did not alter the contractile response of TSM to acetylcholine (ACh) or serotonin. In nine guinea pigs, active tension (AT) caused by 3 x 10(-7) mol/kg of intravenous ACh was 0.74 +/- 0.14 g force per longitudinal length of the segment (g/cm) in the presence of epithelium versus 0.89 +/- 0.16 g/cm after removal of airway epithelium (confirmed histologically) (p NS). The threshold response to ACh was also unchanged (-8.0 +/- 0.3 log mol/kg control versus -8.3 +/- 0.3 log mol/kg after epithelial removal, p NS). In six guinea pigs, the AT caused by 3 x 10(-8) mol/kg of intravenous serotonin was 1.92 +/- 0.63 g/cm with an intact epithelium versus 2.15 +/- 0.70 g/cm after epithelial removal in vivo (p NS). Epithelial removal in vitro increased the sensitivity of TSM contraction to ACh when the data were expressed as the percentage maximal response to ACh. The concentration of ACh causing 50% of the maximal response (EC50) was -5.74 +/- 0.25 log M in eight epithelium-intact TSM strips versus -6.37 +/- 0.16 log M after epithelial removal in controls (n = 8) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Intratracheal E. coli lipopolysaccharide induces platelet-dependent bronchial hyperreactivity.

Bronchial hyperresponsiveness (BHR) characterizes asthma and accompanies respiratory infections. Because endotoxin [lipopolysaccharide (LPS)] induces either hyper- or hyporesponsiveness of the guinea pig airways and protects against bronchopulmonary anaphylaxis in sensitized guinea pigs, we compared the effects of the intratracheal administration of Escherichia coli LPS on bronchopulmonary responsiveness to intravenous serotonin or acetylcholine in sensitized and nonsensitized guinea pigs. LPS (1 mg) induced BHR within 1-2 h, with a threefold increase in the bronchial response after serotonin challenge in both groups (n = 6; P < 0.005) and a marked influx of neutrophils into the perivascular and peribronchial connective tissue and the bronchoalveolar lavage fluid. This BHR was not leukocyte dependent, since it was still observed in animals depleted of circulating leukocytes with vinblastine and was not modified by antineutrophil serum, unless platelet counts were < 100,000/mm3. This suggested that LPS-induced BHR involves platelets, and indeed antiplatelet serum, which depleted platelets, or prostacyclin, which inhibited platelets, was effective in suppressing BHR. Neither aspirin, mepyramine, nor the platelet-activating factor antagonist WEB 2170, administered before LPS instillation, prevented BHR, whereas the association of methysergide, mepyramine, and aspirin was effective, without modifying platelet and leukocyte counts. This association has been shown to prevent the release of ATP by ex vivo platelets. Our results suggest that platelets or a platelet-derived product mediates LPS-induced BHR.

Vagal afferent-mediated inhibition of a nociceptive reflex by i.v. serotonin in the rat. II. Role of 5-HT receptor subtypes

In the rat, intravenous (i.v.) serotonin (5-HT) is a noxious stimulus which produces distinct vagal afferent-mediated pseudoaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the nociceptive tail-flick (TF) reflex and a complex triad of cardiovascular responses. In the present study, we have used a variety of 5-HT receptor antagonists to characterize the receptor subtype(s) in the rat that mediate (1) inhibition of the TF reflex and (2) the cardiovascular responses produced by i.v. 5-HT. 5-HT produced a dose-dependent (3–72 μg/kg, i.v.) inhibition of the TF reflex (ED 50 = 15.3 ± 0.7 μg/kg). Following administration of the 5-HT 2 receptor-selective antagonists ketanserin (50–250 μg/kg, i.v.) or xylamidine (10–100 μg/kg, i.v.), or the 5-HT 3 receptor-selective antagonists ICS 205–930 (50–250 μg/kg, i.v.) or MDL 72222 (25–250 μg/kg, i.v.), there appeared to be a parallel shift of the 5-HT dose-response curve to the right. Following co-administration of xylamidine (50 μg/kg, i.v.) with ICS 205–930 (100 μg/kg, i.v.), the 5-HT-induced inhibition of the TF reflex was completely abolished at all doses of 5-HT tested (3–288 μg/kg, i.v.). In contrast, administration of the centrally acting 5-HT 2 receptor-selective antagonist LY 53857 (10–100 μg/kg, i.v.) or the non-specific receptor antagonist methysergide (25–500 μg/kg, i.v.) resulted in a dose-dependent, but not parallel shift of the 5-HT dose-response curve to the right. The maximal doses of LY 53857 and methysergide tested (250 μg/kg and 500 μg/kg, respectively) completel abolished the effects of 5-HT (3–288 μg/kg, i.v.). Administration of the α 1-adrenoceptor antagonist prazosin (25–100 μg/kg, i.v.) failed to alter the 5-HT dose-response curve, indicating that the effects of ketanserin were due to blockage of 5-HT 2 receptors rather than α 1 receptors. Administration of each of the antagonists also produced marked, but selective effects on components of the complex cardiovascular response to i.v. 5-HT. Each of the 5-HT 3 receptor selective antagonists (ICS 205–930 or MDL 72222) produced a dose-dependent attenuation of the Bezold-Jarisch reflex-mediated hypotension and bradycardia, and each of the 5-HT 2 receptor selective antagonists (xylamidine, ketanserin or LY 53857) produced a dose-dependent attenuation of the pressor response. The non-specific 5-HT receptor antagonist methysergide produced a dose-dependent attenuation of the 5-HT-induced pressor response. Prazosin resulted in a significant increase in the magnitude of the 5-HT-induced Bezold-Jarisch reflex bradycardia. Saline did not alter the cardiovascular response to i.v. 5-HT. Prazosin (100 μg/kg, i.v.) and ketanserin (250 μg/kg, i.v.) significantly lowered resting mean arterial blood pressure while ICS 205–930 (250 μg/kg, i.v.) significantly raised resting mean arterial blood pressure. The results of this study clearly show that i.v. 5-HT-induced inhibition of the TF reflex requires activation of peripheral 5-HT 2 and 5-HT 3 receptors. In addition, these studies raise the possibility that central 5-HT 2 receptors may also be involved in the 5-HT-induced vagally mediated inhibition of the TF reflex.

Anesthetic effects on pulmonary allergic responses in rats: changes in sensitivity to serotonin.

Subsequent to observations that pulmonary responses to antigen challenge are of different magnitudes in sensitized rats that are anesthetized with different drugs, we conducted studies to test whether the alterations in responses were due to changes in airway responsiveness to cholinergic or serotonergic challenge, opioid-receptor mediated events, or changes in mast cell mediator release. Immunoglobulin E-sensitized rats anesthetized with ketamine/urethan had larger changes in lung resistance and plasma histamine after pulmonary antigen challenge compared with rats anesthetized with fentanyl-droperidol. Blockade of opioid receptors with naloxone did not affect the responses. In unsensitized rats, airway responses to aerosolized methacholine were similar for the two anesthetics, indicating unchanged smooth muscle responsiveness; however, airway responses to intravenous serotonin were enhanced by ketamine and ablated by droperidol. We conclude that ketamine- and droperidol-induced alterations of pulmonary allergic responses are due to changes in sensitivity to serotonin and in mast cell mediator release. We speculate that mast cell mediator release may be modulated by a serotonin receptor-linked mechanism.

Functional properties of spinomesencephalic tract (SMT) cells in the upper cervical spinal cord of the cat

Response and receptive field properties were evaluated for 62 spinomesencephalic tract cells in the upper cervical spinal cord (C1–C3) of cats anesthetized with sodium pentobarbital and alpha-chloralose. Recordings were made from cells in laminae I–VIII and X contralateral to antidromic stimulating electrodes positioned in the rostral, caudal and intercollicular region of the midbrain. The mean antidromic threshold for all cells was 185 ± 132 μA, and conduction velocities ranged from 2.3 to 38.6 m/sec. Twelve cells were backfired from both midbrain and diencephalic stimulation sites. Receptive fields ranged from simple i.e., ipsilateral forelimb or face, to complex i.e., excitatory and/or inhibitory responses from large portions of the body. Peripheral receptive fields included muscles, joints, cornea, dura, forelimbs, hind limbs, tail, and/or testicles. Five functional classes of cells were observed: (a) wide dynamic range (14 cells); (b) high threshold (2 cells); (c) low threshold (4 cells); (d) deep/tap (11 cells); and (e) non-responsive (31 cells). Eight cells were evaluated for responses to different doses (5–150 μg) of intravenous (i.v.) serotonin. Two of the 8 cells exhibited excitatory effects, whereas 2 cells classified as deep/tap and 4 cells classified as non-responsive were not affected. The results of this study have shown the upper cervical component of the spinomesencephalic tract is made up of a heterogenous population of cells involved in the integration of varied inputs from large portions of the body. It is proposed that the large population of SMT cells in the upper cervical spinal cord may be involved in pain mechanisms, especially those related to the affective consequences of acute and chronic pain.

Reduced nociceptive effects of intravenous serotonin (5–HT) in the spontaneously hypertensive rat

This study compared the cutaneous (baseline tail-flick (TF) latencies) and visceral nociceptive responses (5-HT-induced inhibition of the TF reflex and pseudaffective responses) in lightly pentobarbital-anesthetized 16 week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). SHR were significantly less sensitive to the nociceptive effect of i.v. 5-HT compared to WKY rats. That is, SHR had a greater quantal ED50 for inhibition of the TF reflex than WKY rats (50.0 and 15.1 micrograms/kg, respectively). SHR also showed the presence of distinct pseudaffective responses (flattening of the ears, closure of the eyes to slits and contraction of the facial musculature) at much greater doses than in WKY rats, thereby paralleling the same changes in sensitivity observed the 5-HT-induced inhibition of the TF reflex. 5-HT-induced similar cardiovascular responses in WKY and SHR except that the SHR showed a significantly greater pressor response compared to WKY rats. These results demonstrate that the SHR show a marked reduction in sensitivity to the nociceptive, but not the cardiovascular, responses to i.v. 5-HT.