Depletion of central beta-endorphin blocks midbrain stimulation produced analgesia in the freely-moving rat.
The present study examines the role of central beta-endorphin in the generation of stimulation-induced analgesia from the ventral midbrain periaqueductal gray of freely-moving rats. Electrical stimulation of the ventral midbrain periaqueductal gray led to an antinociception against noxious heat which gradually subsided post-stimulation over a period of about 15 min. Locomotor effects (ipsilateral rotation) were also seen which were not correlated in intensity with the analgesia and which disappeared immediately with termination of stimulation. There was no indication of any aversive effects. Application of the opioid antagonist, naloxone, 10 min pre-stimulation, strongly attenuated the antinociception without changing basal thresholds. It did not influence the locomotor changes. Bilateral, radiofrequency lesions of the mediobasal arcuate hypothalamus greatly depleted immunoreactive beta-endorphin from brain tissues without affecting its levels in plasma. Lesioned rats showed a pronounced reduction of stimulation-produced antinociception in the absence of any change in basal thresholds; the locomotor effects of stimulation were not influenced. The degree of depletion of immunoreactive-beta-endorphin significantly correlated with the degree of attenuation of antinociception. These data suggest: stimulation of the ventral midbrain periaqueductal gray leads both to an antinociception and locomotor effects in freely-moving rats: these can be clearly dissociated from each other; the antinociception (but not locomotor effects) are mediated by an endogenous opioid sensitive to blockade by naloxone; and central beta-endorphin may be the endogenous opioid mediating stimulation-produced antinociception from the ventral midbrain periaqueductal gray in the rat.
D000698:Analgesia; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004558:Electric Stimulation; D004598:Electrosurgery; D004723:Endorphins / Q000378:metabolism / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D001615:beta-Endorphin
D004723:Endorphins; D009270:Naloxone; D001615:beta-Endorphin