RELEASE INTO VENTRICULOCISTERNAL PERFUSATE OF BETA-ENDORPHIN-IMMUNOREACTIVITY AND MET-ENKEPHALIN-IMMUNOREACTIVITY - EFFECTS OF ELECTRICAL-STIMULATION IN THE ARCUATE NUCLEUS AND PERIAQUEDUCTAL GRAY OF THE RAT

To examine the resting and evoked release of the endogenous opioid peptides beta-endorphin and Met-enkephalin from brain, we examined the levels of the respective immunoreactivities in the lateral ventricle-cisterna magna perfusate of the halothane-anesthetized rat. Ten Hz but not 100 Hz stimulation in the arcuate nucleus (ARC) of the hypothalamus released beta-endorphin immunoreactivity (beta-EPir) to the perfusate, whereas 100 Hz but not 10 Hz stimulation in the periaqueductal gray (FAG) of the mid brain released Met-enkephalin immunoreactivity (MEir). MEir was not released by stimulation in ARC and beta-EPir was not released by stimulation in FAG. Characterization of the released beta-EPir and MEir by high performance liquid chromatography showed that authentic beta-endorphin and Met-enkephalin were the major constituents of beta-EPir and MEir, respectively. Systemic administration of the dopaminergic antagonist haloperidol increased plasma, but not perfusate levels of beta-EPir. Both the opioid antagonist naloxone and the NMDA antagonist MK-801 failed to affect beta-EPir or MEir release. ARC and FAG stimulation inhibited a nociceptive reflex (tail-dip in 52.5 degrees C water), and naloxone did not reliably reverse this inhibition. These data support the previously suggested possibility of opioid mediation of stimulation induced analgesia, although we were unable to confirm the theory by naloxone reversibility in this study. Furthermore, the data support the assumption that measurement of opioid peptides in cerebrospinal fluid is a relevant approach in research aimed at elucidating the physiological and pathophysiological roles of endogenous opioid peptides.