Forebrain sites differentially sensitive to beta-endorphin and morphine for analgesia and release of Met-enkephalin in the pentobarbital-anesthesized rat

Abstract

The mapping of the forebrain regions sensitive to beta-endorphin and morphine for antinociception was performed in pentobarbital-anesthetized rats. The antinociception was assessed by the tail-flick test. The sites most sensitive to beta-endorphin (2 micrograms) for inhibition of the tail-flick response were located in the ventromedial regions of the forebrain such as medial posterior nucleus accumbens, medial preoptic area and arcuate hypothalamic nucleus. Other areas such as anterior nucleus accumbens, dorsomedial hypothalamic nucleus, posterior hypothalamus, lateral hypothalamus, caudate nuclei, thalami and cerebral cortex were not sensitive to beta-endorphin for the tail-flick inhibition. The sites sensitive to morphine sulfate (4 micrograms) for inhibition of the tail-flick response were located in regions of medial preoptic nucleus and arcuate hypothalamic nucleus. Posterior nucleus accumbens, which is sensitive to beta-endorphin, was not sensitive to morphine for antinociception. Morphine injected into this site did not produce tail-flick inhibition in both conscious and pentobarbital-anesthetized rats. The inhibition of the tail-flick response induced by beta-endorphin (2 micrograms) from posterior nucleus accumbens, medial preoptic area and arcuate hypothalamic nucleus was blocked by the administration of beta-endorphin-(1-27), an epsilon opioid receptor blocker, but not by D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2, a mu opioid receptor blocker. On the other hand, the inhibition induced by morphine (4 micrograms) from medial preoptic area and arcuate hypothalamic nucleus was blocked by D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2, but not by beta-endorphin-(1-27).(ABSTRACT TRUNCATED AT 250 WORDS)