RESUMEN
Central oxytocin plays an important role in regulating emotionality. The amygdala expresses gonadal steroid-sensitive oxytocin binding sites in both the central and medial sub-nuclei, although the densities markedly differ between these nuclei. These studies examined the in vitro electrophysiological effects of oxytocin in the two amygdaloid nuclei and compared responses in female rats in different reproductive states (virgin, pregnant and lactating). Oxytocin (10(-9)-10(-6)M) caused a concentration-dependent increase in the firing rate of 20-36% of the neurones in both nuclei. Although autoradiographic studies using the oxytocin receptor antagonist [(125)I]d(CH(2))(5)[Tyr(Me)(2),Thr(4),Orn(8),Tyr-NH(2)(9)]-vasotocin showed a higher density of binding in the central nucleus of the amygdala than medial nucleus of the amygdala, neurones in the central nucleus of the amygdala had a much lower sensitivity to oxytocin: equivalent responses obtained with 10(-6)M in the central nucleus of the amygdala and 10(-8)M in the medial nucleus of the amygdala, and neurones in the central nucleus of the amygdala were insensitive to concentrations below 10(-6)M. Furthermore, repeated applications of oxytocin induced homologous desensitization in the central nucleus of the amygdala, but not medial nucleus of the amygdala-a single application of oxytocin producing long duration suppression of responses. This indicates that oxytocin has contrasting modes of action in the amygdala. Studies made across the reproductive cycle showed that lactating animals exhibited a larger proportion of oxytocin-responsive neurones in the medial nucleus of the amygdala and a smaller proportion in the central nucleus of the amygdala, compared with virgin or pregnant animals, indicating a peripartum shift in relative activation within the amygdala. However, changes in responses were not accompanied by changes in the density of oxytocin binding sites. These data show that oxytocin has a markedly different efficacy on neuronal activation in the central and medial sub-nuclei of the amygdala. The relative shift in excitatory responses between these two nuclei may underlie some of the neuroendocrine, behavioral and anxiolytic effects which have been ascribed to oxytocin in the periparturient rat.
Asunto(s)
Amígdala del Cerebelo/citología , Neuronas/efectos de los fármacos , Oxitocina/farmacología , Potenciales de Acción/efectos de los fármacos , Análisis de Varianza , Animales , Autorradiografía/métodos , Relación Dosis-Respuesta a Droga , Femenino , Técnicas In Vitro , Isótopos de Yodo/farmacocinética , Lactancia/efectos de los fármacos , Lactancia/fisiología , Neuronas/fisiología , Embarazo , Unión Proteica , Ratas , Ratas WistarRESUMEN
The effects of intraperitoneal administration of antagonists to morphine, norepinephrine, acetylcholine, dopamine and 5-hydroxytryptamine (5-HT) have been studied on the antinociceptive effect of electrical stimulation of the rat habenular complex (HbC). The antinociceptive effect of agonists microinjected into the HbC was also examined. A 15-s period of 53 microA rms sine-wave stimulation of the HbC significantly increased the latency of the tail-flick reflex to noxious heat for periods of up to 15 min. This effect was significantly attenuated by pretreating rats with naloxone (1 mg/kg) or phenoxybenzamine (5 mg/kg). Methysergide (5 mg/kg), haloperidol (5 mg/kg), atropine (1 mg/kg), and mecamylamine (1 mg/kg) had little effect on the antinociceptive effect of HbC stimulation. L-Glutamate (3.5 and 7.0 micrograms), morphine (1.0 and 5.0 micrograms), and carbachol (0.4 and 0.8 micrograms), but not 5-HT (5 micrograms), dopamine (5 micrograms) or norepinephrine (5 micrograms), induced a dose-dependent increase in the tail-flick latency when microinjected into the HbC. The effect of carbachol was significantly attenuated in rats previously treated with intraperitoneal administration of atropine or mecamylamine and fully depressed in rats previously treated with a combination of these two cholinergic antagonists. It is concluded that antagonists of opiate receptors and alpha-adrenoceptors, but not dopamine or cholinergic receptors, reduce the antinociceptive effects of HbC stimulation. These observations differ from the reported effects of these antagonists on the antinociception caused by stimulating the periaqueductal gray, but resemble the antinociception caused by stimulating the ventrolateral medulla and locus coeruleus.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Dolor/fisiopatología , Glándula Pineal/fisiología , Animales , Estimulación Eléctrica , Masculino , Microinyecciones , Antagonistas Muscarínicos , Antagonistas de Narcóticos/farmacología , Antagonistas Nicotínicos , Dimensión del Dolor/métodos , Glándula Pineal/efectos de los fármacos , Ratas , Ratas Endogámicas , Antagonistas de la Serotonina/farmacologíaRESUMEN
The changes in the tail-flick latency to noxious heat stimulation and in the threshold for defensive/affective reactions to noxious pressure of the skin were studied following electrical stimulation of the habenular complex (HbC) and adjacent brain structures in the male rat. Single brief (15 s), low intensity (53 microA r.m.s.) stimulation of the HbC caused no significant increase in the locomotor activity or motor deficit but induced a potent and short-lasting antinociception as revealed by both algesimetric tests. Animals stimulated in the HbC also displayed poor avoidance learning in a conditioned place preference paradigm, thus suggesting that aversion is unlikely to determine antinociception. Rats daily stimulated in the HbC became tolerant to the antinociception induced by HbC stimulation or to a high systemic dose of morphine (6 mg/kg i.p.). These results indicate that stimulation of the HbC may increase the thresholds of spinally and supraspinally integrated reflexes, thus supporting the hypothesis that this nucleus may play a role in pain control, probably involving an opioid-dependent mechanism.