RESUMEN
A number of studies suggest the involvement of glutamate in central hyperalgesia through NMDA receptors in animal models of inflammation. Most studies analyze glutamate effects at the spinal cord level. In this work, the effects of morphine, dizocilpine and riluzole on the hyperalgesia induced by carrageenan administration in the rat paw model were investigated. The effects of morphine and riluzole on the release of glutamate and aspartate and on the concentrations of citrulline and arginine in dialysates of the ventral posterolateral nucleus of the thalamus were also examined. All three drugs decreased hyperalgesia when administered prior to carrageenan injection. Morphine decreased the glutamate concentration in dialysates of the ventral posterolateral nucleus but did not affect the concentrations of the other amino acids. The effect of morphine was observed in the absence of painful stimulation and when pressure applied to the rat paw induced a nociceptive reaction. Riluzole decreased the concentrations of glutamate and aspartate and those of citrulline and arginine in the presence or absence of painful stimulation. These experiments suggest that morphine and riluzole attenuate the hyperalgesia induced by injection of carrageenan in the rat hind paw, at least partly, by decreasing glutamate release in the ventral posterolateral thalamic nucleus.
Asunto(s)
Maleato de Dizocilpina/farmacología , Hiperalgesia/prevención & control , Morfina/farmacología , Riluzol/farmacología , Núcleos Talámicos/efectos de los fármacos , Análisis de Varianza , Animales , Arginina/efectos de los fármacos , Arginina/metabolismo , Ácido Aspártico/efectos de los fármacos , Ácido Aspártico/metabolismo , Carragenina/efectos adversos , Citrulina/efectos de los fármacos , Citrulina/metabolismo , Soluciones para Diálisis/química , Relación Dosis-Respuesta a Droga , Ácido Glutámico/efectos de los fármacos , Ácido Glutámico/metabolismo , Miembro Posterior , Hiperalgesia/inducido químicamente , Masculino , Microdiálisis , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Wistar , Núcleos Talámicos/químicaRESUMEN
Excitatory amino acids release during morphine or naloxone administration was studied in rats. Microdialysis in freely moving animals and capillary electrophoresis with laser-induced fluorescence detection were used to measure several amino acids including glutamate and aspartate in the extracellular fluid at the nucleus accumbens. Perfusion with a calcium-free Ringer's solution decreased glutamate and aspartate in nucleus accumbens dialysates to 35% of its baseline levels, suggesting partial synaptic origin of these amino acids. The first morphine injection decreased glutamate and aspartate to 50% of its baseline level. After repeated morphine injections this effect disappeared, suggesting tolerance. Naloxone injections to morphine-dependent rats increased 300% glutamate and aspartate release; these experiments suggest that excitatory amino acid release in the nucleus accumbens might play a role in morphine withdrawal.
Asunto(s)
Ácido Aspártico/metabolismo , Ácido Glutámico/metabolismo , Morfina/toxicidad , Núcleo Accumbens/metabolismo , Síndrome de Abstinencia a Sustancias/metabolismo , Animales , Calcio/metabolismo , Espacio Extracelular/metabolismo , Masculino , Microdiálisis , Morfina/administración & dosificación , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Núcleo Accumbens/efectos de los fármacos , Ratas , Ratas Wistar , Síndrome de Abstinencia a Sustancias/etiologíaRESUMEN
In the present experiment the combination of brain microdialysis and CZE-LIFD permitted the measurement of glutamate in 100 nl microdialysis samples collected every 5 or 6 s. Samples were collected every 6 s, in rats anesthetized with two different anesthetic agents (ketamine and sodium thiopental). A microdialysis probe was inserted in the cortex of an anesthetized rat in the territory irrigated by the middle cerebral artery. The artery was clamped for 30 s and then released. The samples were derivatized with fluorescein isothiocyanate I (FITC) by means of a continuous-flow reactor, collected and injected into a home-made CZE-LIFD instrument. Glutamate decreased immediately after clamping the artery in ketamine anesthetized rats and increased 1 min after the onset of the ischemia in sodium thiopental anesthetized rats. In another experiment a 60 mM KCl solution was injected through a microdialysis probe inserted in the hippocampus of an anesthetized rat. In the first 5 s after the KCl solution reached the tissue, glutamate increased but gamma-aminobutytic acid and glutamine did not. The experiments show that time resolution of brain microdialysis can be reduced to a few seconds if the analytical technique is the proper one.
Asunto(s)
Encéfalo/metabolismo , Ácido Glutámico/análisis , Microdiálisis , Animales , Isquemia Encefálica/metabolismo , Soluciones para Diálisis/química , Electroforesis Capilar , Rayos Láser , Masculino , Ratas , Ratas Wistar , Espectrometría de Fluorescencia , Factores de TiempoRESUMEN
In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.