RESUMEN
The zona incerta (ZI) is a subthalamic nucleus connected to several structures, some of them known to be involved with antinociception. The ZI itself may be involved with both antinociception and nociception. The antinociceptive effects of stimulating the ZI with glutamate using the rat tail-flick test and a rat model of incision pain were examined. The effects of intraperitoneal antagonists of acetylcholine, noradrenaline, serotonin, dopamine, or opioids on glutamate-induced antinociception from the ZI in the tail-flick test were also evaluated. The injection of glutamate (7 µg/0.25 µl) into the ZI increased tail-flick latency and inhibited post-incision pain, but did not change the animal performance in a Rota-rod test. The injection of glutamate into sites near the ZI was non effective. The glutamate-induced antinociception from the ZI did not occur in animals with bilateral lesion of the dorsolateral funiculus, or in rats treated intraperitoneally with naloxone (1 and 2 m/kg), methysergide (1 and 2 m/kg) or phenoxybenzamine (2 m/kg), but remained unchanged in rats treated with atropine, mecamylamine, or haloperidol (all given at doses of 1 and 2 m/kg). We conclude that the antinociceptive effect evoked from the ZI is not due to a reduced motor performance, is likely to result from the activation of a pain-inhibitory mechanism that descends to the spinal cord via the dorsolateral funiculus, and involves at least opioid, serotonergic and α-adrenergic mechanisms. This profile resembles the reported effects of these antagonists on the antinociception caused by stimulating the periaqueductal gray or the pedunculopontine tegmental nucleus.
Asunto(s)
Analgésicos/administración & dosificación , Ácido Glutámico/administración & dosificación , Dolor/tratamiento farmacológico , Subtálamo/efectos de los fármacos , Animales , Atropina/administración & dosificación , Haloperidol/administración & dosificación , Masculino , Mecamilamina/administración & dosificación , Metisergida/administración & dosificación , Microinyecciones , Naloxona/administración & dosificación , Dolor/patología , Dolor/fisiopatología , Dimensión del Dolor , Fenoxibenzamina/administración & dosificación , Ratas , Ratas Wistar , Núcleo Subtalámico/efectos de los fármacos , Núcleo Subtalámico/patología , Núcleo Subtalámico/fisiopatología , Subtálamo/patología , Subtálamo/fisiopatologíaRESUMEN
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 formalin 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 formalin 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%. 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.
Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Metisergida/farmacología , Nociceptores/efectos de los fármacos , Nociceptores/fisiología , Dolor/fisiopatología , Fentolamina/farmacología , Antagonistas de la Serotonina/farmacología , Antagonistas Adrenérgicos alfa/administración & dosificación , Animales , Masculino , Metisergida/administración & dosificación , Fentolamina/administración & dosificación , Ratas , Ratas Wistar , Antagonistas de la Serotonina/administración & dosificación , Espacio SubaracnoideoRESUMEN
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.
Asunto(s)
Animales , Ratas , Masculino , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas de la Serotonina/farmacología , Espacio Subaracnoideo/anatomía & histología , Fentolamina/farmacología , Metisergida , Metisergida/farmacología , Nociceptores/efectos de los fármacos , Nociceptores/fisiología , Dimensión del Dolor , Dolor/fisiopatología , Fentolamina/farmacología , Antagonistas de la Serotonina/farmacología , Antagonistas Adrenérgicos alfa/administración & dosificación , Metisergida/administración & dosificación , Fentolamina/administración & dosificación , Ratas Wistar , Espacio Subaracnoideo , Antagonistas de la Serotonina/administración & dosificaciónRESUMEN
This study investigated the involvement of serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) in the control of sodium (Na+) excretion, potassium (K+) excretion, and urinary volume in unanesthetized rats subjected to acute isotonic blood volume expansion (0.15 M NaCl, 2 ml/100 g of body wt over 1 min) or control rats. Plasma oxytocin (OT), vasopressin (VP), and atrial natriuretic peptide (ANP) levels were also determined in the same protocol. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In rats treated with vehicle in the LPBN, blood volume expansion increased urinary volume, Na+ and K+ excretion, and also plasma ANP and OT. Bilateral injections of serotonergic receptor antagonist methysergide (1 or 4 microg/200 etal) into the LPBN reduced the effects of blood volume expansion on increased Na+ and K+ excretion and urinary volume, while LPBN injections of serotonergic 5-HT(2a)/HT(2c) receptor agonist, 2.5-dimetoxi-4-iodoamphetamine hydrobromide (DOI; 1 or 5 microg/200 etal) enhanced the effects of blood volume expansion on Na+ and K+ excretion and urinary volume. Methysergide (4 microg) into the LPBN decreased the effects of blood volume expansion on plasma ANP and OT, while DOI (5 microg) increased them. The present results suggest the involvement of LPBN serotonergic mechanisms in the regulation of urinary sodium, potassium and water excretion, and hormonal responses to acute isotonic blood volume expansion.
Asunto(s)
Anfetaminas/farmacología , Volumen Sanguíneo , Metisergida/farmacología , Puente/fisiología , Receptores de Serotonina 5-HT2/fisiología , Cloruro de Sodio Dietético/farmacología , Anfetaminas/administración & dosificación , Animales , Factor Natriurético Atrial/sangre , Relación Dosis-Respuesta a Droga , Conducta de Ingestión de Líquido/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Metisergida/administración & dosificación , Microinyecciones , Oxitocina/sangre , Puente/efectos de los fármacos , Potasio/orina , Ratas , Ratas Wistar , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/farmacología , Sodio/orina , Factores de Tiempo , Vasopresinas/sangreRESUMEN
Recent studies have shown the existence of two important inhibitory mechanisms for the control of NACL and water intake: one mechanism involves serotonin in the lateral parabrachial nucleus (LPBN) and the other depends on alpha(2)-adrenergic/imidazoline receptors probably in the forebrain areas. In the present study we investigated if alpha(2)-adrenergic/imidazoline and serotonergic inhibitory mechanisms interact to control NaCl and water intake. Male Holtzman rats with cannulas implanted simultaneously into the lateral ventricle (LV) and bilaterally into the LPBN were used. The ingestion of 0.3 M NaCl and water was induced by treatment with the diuretic furosemide (10 mg/kg of body weight)+the angiotensin converting enzyme inhibitor captopril (5 mg/kg) injected subcutaneously 1 h before the access of rats to water and 0.3 M NaCl. Intracerebroventricular (i.c.v.) injection of the alpha(2)-adrenergic/imidazoline agonist clonidine (20 nmol/1 microl) almost abolished water (1.6+/-1.2, vs. vehicle: 7.5+/-2.2 ml/2 h) and 0.3 M NaCl intake (0.5+/-0.3, vs. vehicle: 2.2+/-0.8 ml/2 h). Similar effects were produced by bilateral injections of the 5HT(2a/2c) serotonergic agonist 2,5-dimetoxy-4-iodoamphetamine (DOI, 5 microg/0.2 microl each site) into the LPBN on water (3.6+/-0.9 ml/2 h) and 0.3 M NaCl intake (0.4+/-0.2 ml/2 h). Injection of the alpha(2)-adrenergic/imidazoline antagonist idazoxan (320 nmol) i.c.v. completely blocked the effects of clonidine on water (8.4+/-1.5 ml/2 h) and NaCl intake (4.0+/-1.2 ml/2 h), but did not change the effects of LPBN injections of DOI on water (4.2+/-1.0 ml/2 h) and NaCl intake (0.7+/-0.2 ml/2 h). Bilateral injections of methysergide (4 microg/0.2 microl each site) into the LPBN increased 0.3 M NaCl intake (6.4+/-1.9 ml/2 h), not water intake. The inhibitory effect of i.c.v. clonidine on water and 0.3 M NaCl was still present after injections of methysergide into the LPBN (1.5+/-0.8 and 1.7+/-1.4 ml/2 h, respectively). The results show that the inhibitory effects of the activation of alpha(2)-adrenergic/imidazoline receptors in the forebrain are still present after blockade of the LPBN serotonergic mechanisms and vice versa for the activation of serotonergic mechanisms of the LPBN. Therefore, each system may act independently to inhibit NaCl and water intake.
Asunto(s)
Conducta de Ingestión de Líquido/fisiología , Ingestión de Líquidos/fisiología , Receptores de Droga/fisiología , Receptores de Serotonina/fisiología , Cloruro de Sodio Dietético , Anfetaminas/administración & dosificación , Anfetaminas/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Captopril/farmacología , Núcleos Cerebelosos/efectos de los fármacos , Núcleos Cerebelosos/fisiología , Clonidina/administración & dosificación , Clonidina/farmacología , Diuréticos/farmacología , Ingestión de Líquidos/efectos de los fármacos , Conducta de Ingestión de Líquido/efectos de los fármacos , Furosemida/farmacología , Idazoxan/administración & dosificación , Idazoxan/farmacología , Receptores de Imidazolina , Inyecciones Intraventriculares , Masculino , Metisergida/administración & dosificación , Metisergida/farmacología , Ratas , Ratas Sprague-Dawley , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/farmacologíaRESUMEN
RATIONALE: Electrical stimulation of the dorsal periaqueductal gray matter (dPAG) and the inferior colliculus (IC) has been used as an aversive unconditioned stimulus. However, studies on the behavioral, sensorial and autonomic components of the conditioned fear elaborated in the midbrain tectum are lacking. OBJECTIVES: This study was undertaken to investigate the nature of the aversiveness of stimulation of the dPAG and IC as well as the modulation by 5-HT mechanisms of the fear conditioned responses to these stimulations. METHODS: Animals chronically implanted with an electrode glued to a guide cannula into the dPAG or the IC were submitted to one, two or three sessions of conditioning. Each session consisted of ten pairings of the light in a distinctive chamber (CS) with the electrical stimulation of one of these regions at the escape threshold determined previously. Control groups were submitted to the same procedure, except for the conditioning sessions in which the conditioned stimuli were presented alone in one case and performed in a different context in the other. On the next day, each animal was exposed only to the CS (testing) and the duration of freezing, number of rearings, grooming, bouts of micturition and fecal boli were recorded for 5 min. Before and after the testing session, the animals were submitted to the tail-flick test. RESULTS: The data showed that the conditioning with electrical stimulation of the dPAG and the IC caused significant increases in the time of freezing, defecation and micturition, and significant reductions in the number of rearings and grooming. On the other hand, only the conditioning with electrical stimulation of the dPAG produced significant conditioned antinociception. Microinjections of methysergide, a non-specific antagonist of 5-HT receptors, or ketanserin, an antagonist of 5-HT2A receptors, into the dPAG before testing significantly inhibited the antinociception without affecting any of the behavioral or autonomic conditioned responses. CONCLUSIONS: 1) Conditioned freezing may be produced using the electrical stimulation of the dPAG or IC as unconditioned stimuli, 2) only the pairing of CS plus dPAG but not with IC stimulation, produces significant conditioned antinociception, 3) blockade of 5-HT2A receptors inhibits conditioned antinociception but not the conditioned defensive behavior using the electrical stimulation of the dPAG as unconditioned stimulus.
Asunto(s)
Conducta Animal/fisiología , Condicionamiento Psicológico/fisiología , Colículos Inferiores/fisiología , Dolor/psicología , Sustancia Gris Periacueductal/fisiología , Receptores de Serotonina/fisiología , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Condicionamiento Psicológico/efectos de los fármacos , Estimulación Eléctrica , Ketanserina/farmacología , Masculino , Metisergida/administración & dosificación , Metisergida/farmacología , Microinyecciones , Dimensión del Dolor/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT2A , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/farmacología , Techo del Mesencéfalo/fisiologíaRESUMEN
Serotonin [5-hydroxytryptamine (5-HT)] and CCK injected into the lateral parabrachial nucleus (LPBN) inhibit NaCl and water intake. In this study, we investigated interactions between 5-HT and CCK into the LPBN to control water and NaCl intake. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were treated with furosemide + captopril to induce water and NaCl intake. Bilateral LPBN injections of high doses of the 5-HT antagonist methysergide (4 microg) or the CCK antagonist proglumide (50 microg), alone or combined, produced similar increases in water and 1.8% NaCl intake. Low doses of methysergide (0.5 microg) + proglumide (20 microg) produced greater increases in NaCl intake than when they were injected alone. The 5-HT(2a/2c) agonist 2,5-dimetoxy-4-iodoamphetamine hydrobromide (DOI; 5 microg) into the LPBN reduced water and NaCl intake. After proglumide (50 microg) + DOI treatment, the intake was not different from vehicle treatment. CCK-8 (1 microg) alone produced no effect. CCK-8 combined with methysergide (4 microg) reduced the effect of methysergide on NaCl intake. The data suggest that functional interactions between 5-HT and CCK in the LPBN may be important for exerting inhibitory control of NaCl intake.
Asunto(s)
Apetito/fisiología , Núcleos Talámicos Intralaminares/fisiología , Serotonina/farmacología , Sincalida/análogos & derivados , Sincalida/farmacología , Sodio en la Dieta , Anfetaminas/farmacología , Animales , Apetito/efectos de los fármacos , Interacciones Farmacológicas , Homeostasis , Núcleos Talámicos Intralaminares/efectos de los fármacos , Masculino , Metisergida/administración & dosificación , Metisergida/farmacología , Microinyecciones , Modelos Neurológicos , Neuronas/efectos de los fármacos , Neuronas/fisiología , Proglumida/farmacología , Ratas , Ratas Sprague-Dawley , Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/farmacología , Sincalida/administración & dosificaciónRESUMEN
The neural mechanisms involved in post-ictal analgesia remain to be elucidated. Pentylenetetrazol (PTZ) is used experimentally to induce seizure in animal subjects. This non-competitive antagonist blocks GABA-mediated Cl(-) flux. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significant increase in the tail-flick latencies (TFL), at least for 30 min of the post-ictal period. Peripheral administration of naloxone (5 mg/kg and 10 mg/kg), atropine (1 mg/kg and 5 mg/kg), methysergide (1 mg/kg and 5 mg/kg) and ketanserine (1 mg/kg and 2 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. However, while naloxone antagonized analgesia 15 and 25 min post convulsions, the other drugs caused a blockade of the post-ictal analgesia in a relatively greater period of time. These results indicate that endogenous opioids, serotonin and acetylcholine may be involved in post-ictal analgesia.
Asunto(s)
Analgesia , Antagonistas Muscarínicos/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Convulsiones/metabolismo , Antagonistas de la Serotonina/administración & dosificación , Animales , Atropina/administración & dosificación , Convulsivantes , Modelos Animales de Enfermedad , Inyecciones Intraperitoneales , Ketanserina/administración & dosificación , Metisergida/administración & dosificación , Actividad Motora/efectos de los fármacos , Naloxona/administración & dosificación , Dimensión del Dolor/efectos de los fármacos , Pentilenotetrazol , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Reflejo/efectos de los fármacos , Convulsiones/inducido químicamente , Convulsiones/fisiopatologíaRESUMEN
It has been shown that the serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) inhibit NaCl intake in different models of angiotensin II (ANG II)-dependent NaCl intake in rats. However, there is no information about the involvement of LPBN serotonergic mechanisms on NaCl intake in a model of NaCl intake not dependent on ANG II like deoxycorticosterone (DOCA)-induced NaCl intake. Therefore, in this study we investigated the effects of bilateral injections of serotonergic agonist and antagonist into the LPBN on DOCA-induced 1.8% NaCl intake in rats. Male Holtzman rats were treated with s.c. DOCA (10 mg/rat each every 3 days). After a period of training, in which the rats had access to 1.8% NaCl during 2 h for several days, the rats were implanted with stainless steel cannulas bilaterally into the LPBN. Bilateral injections of the serotonergic receptor antagonist methysergide (4 microg/0.2 microl each site) in the LPBN increased 1.8% NaCl intake (32.2+/-3.9 versus vehicle: 15.0+/-1.6 ml/2 h, n=10) and water intake (12.5+/-3.5 versus vehicle: 3.2+/-1.0 ml/2 h). Injections of the serotonergic 5HT(2A/2C) receptor agonist DOI (5 microg/0,2 microl each site) in the LPBN reduced 1.8% NaCl intake (6.8+/-1.7 versus saline: 12.4+/-1. 9 ml/2 h, n=10) and water intake (2.2+/-0.8 versus saline: 4.4+/-1.0 ml/2 h). Besides the previously demonstrated importance for the control of ANG II-dependent water and NaCl intake, the data show that the serotonergic inhibitory mechanisms of the LPBN are also involved in the control of DOCA-induced NaCl intake.
Asunto(s)
Anfetaminas/farmacología , Núcleos Cerebelosos/fisiología , Desoxicorticosterona/farmacología , Conducta de Ingestión de Líquido/fisiología , Conducta Alimentaria/fisiología , Metisergida/farmacología , Agonistas de Receptores de Serotonina/farmacología , Serotonina/fisiología , Sodio en la Dieta , Anfetaminas/administración & dosificación , Animales , Presión Sanguínea/efectos de los fármacos , Núcleos Cerebelosos/efectos de los fármacos , Desoxicorticosterona/administración & dosificación , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Metisergida/administración & dosificación , Microinyecciones , Ratas , Ratas Sprague-DawleyRESUMEN
In the present study we have investigated some of the mechanisms underlying B(1) kinin receptor-induced paw edema formation in rats that had been treated with LPS, paying special attention to the involvement of neurogenic inflammation. Intradermal (i.d.) injection of the B(1) receptor agonist des-Arg(9)-BK (100 nmol/paw) resulted in a marked increase in paw volume in animals pre-treated with LPS (0.40+/-0.06 ml). The co-injection of the selective NK(1) FK888 (1 nmol/paw) or NK(2) SR 48968 (3 nmol/paw) receptor antagonists resulted in a significant inhibition of the edema induced by des-Arg(9)-BK (30+/-4 and 25+/-7%, respectively). The NK(3) SR 142801 (3 nmol/paw) antagonist did not demonstrate any significant effect on B(1) receptor-mediated paw edema. The edema induced by des-Arg(9)-BK was also significantly inhibited (33+/-5%) by the co-injection of the CGRP-receptor antagonist CGRP 8-37 (1 nmol/paw) or by treatment of animals with capsaicin (50 mgkg(-1), s.c., 48 h, prior) (45+/-4%). The pre-treatment of animals with methysergide or with mianserin, 5-HT(1) and 5HT(2) antagonists, respectively (both 10 mgkg(-1), i.p. 30 min), resulted in a significant reduction of the edema mediated by B(1) receptors (23+/-5 and 20+/-3%, respectively). In addition, compound 48/80 (12 microg/paw, 24 h) significantly reduced des-Arg(9)-induced paw edema in rats pre-treated with LPS (23+/-3%), while the treatment of animals with the H(1) receptor antagonist pyrilamine (10 mgkg(-1), i.p., 30 min) failed to affect the edematogenic responses involving B(1) receptors. Finally, the co-injection of NOS inhibitors L-NAME (100 nmol/paw) or 7-NINA (10 nmol/paw) did not affect the rat paw edema caused by des-Arg(9)-BK, whereas they significantly inhibited BK-induced paw edema. Jointly, the results of the present study show that the edematogenic response mediated by the activation of B(1) receptors, in animals pre-treated with LPS, involves the release of tachykinins and CGRP, as well as serotonin, while NO and histamine seem not to be involved. Therefore, these data further support the notion that B(1) receptors have an important role in modulating the inflammatory processes.
Asunto(s)
Bradiquinina/análogos & derivados , Lipopolisacáridos/inmunología , Receptores de Bradiquinina/agonistas , Animales , Benzamidas/administración & dosificación , Benzamidas/metabolismo , Bradiquinina/administración & dosificación , Bradiquinina/inmunología , Péptido Relacionado con Gen de Calcitonina/administración & dosificación , Péptido Relacionado con Gen de Calcitonina/metabolismo , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina , Capsaicina/administración & dosificación , Capsaicina/metabolismo , Edema/inducido químicamente , Edema/inmunología , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/metabolismo , Lipopolisacáridos/administración & dosificación , Masculino , Metisergida/administración & dosificación , Metisergida/metabolismo , Mianserina/administración & dosificación , Mianserina/metabolismo , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/metabolismo , Antagonistas del Receptor de Neuroquinina-1 , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/metabolismo , Piperidinas/administración & dosificación , Piperidinas/metabolismo , Pirazoles/administración & dosificación , Pirazoles/metabolismo , Piridinas/administración & dosificación , Piridinas/metabolismo , Pirilamina/administración & dosificación , Pirilamina/metabolismo , Ratas , Ratas Wistar , Receptor de Bradiquinina B1 , Receptores de Neuroquinina-2/antagonistas & inhibidores , Receptores de Neuroquinina-3/antagonistas & inhibidores , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/metabolismo , p-Metoxi-N-metilfenetilamina/administración & dosificación , p-Metoxi-N-metilfenetilamina/metabolismoRESUMEN
This study investigated the effects of bilateral injections of a serotonin (5-HT) receptor agonist into the lateral parabrachial nucleus (LPBN) on the intake of NaCl and water induced by 24-h water deprivation or by sodium depletion followed by 24 h of sodium deprivation (injection of the diuretic furosemide plus 24 h of sodium-deficient diet). Rats had stainless steel cannulas implanted bilaterally into the LPBN. Bilateral LPBN injections of the serotonergic 5-HT1/2 receptor antagonist methysergide (4 micrograms/200 nl at each site) increased hypertonic NaCl intake when tested 24 h after sodium depletion and after 24 h of water deprivation. Water intake also increased after bilateral injections of methysergide into the LPBN. In contrast, the intake of a palatable solution (0.06 M sucrose) under body fluid-replete conditions was not changed after bilateral LPBN methysergide injections. The results show that serotonergic mechanisms in the LPBN modulate water and sodium intake induced by volume depletion and sodium loss. The finding that sucrose intake was not affected by LPBN serotonergic blockade suggests that the effects of the methysergide treatment on the intakes of water and NaCl are not due to a mechanism producing a nonspecific enhancement of all ingestive behaviors.