Attenuating effects of morphine on stress-induced increases in noradrenaline turnover in rat brain regions - Naloxone reversal and behavioral significance

Abstract

By measuring simultaneously levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-S04), in rat brain regions, we have demonstrated that morphine attenuates stress-induced increases in NA turnover selectively in the hypothalamus, amygdala,thaiamus, hippocampus and midbrain. The present study was undertaken to investigate naloxone reversal of these morphine effects and relationship between these effects and hyperemotional ity evoked by stress. Male Wistar rats were exposed to 1-hr immobilization stress. Either naloxone, 0.5 mg/kg or 5 mg/kg, or saline and morphine 6 mg/kg were injected 10 min and 5 min before stress, respectively. MHPG-S04 levels in the five brain regions were determined fluorometrically. Attenuating effects of morphine on stress-induced increases in NA turnover were antagonized by both doses of naloxone in the hypothalamus and amygdala and only by 5 mg/kg of the drug in the thalamus and hippocampus, but not by either dose in the midbrain. Naloxone at 5 mg/kg significantly enhanced struggling and defecation during 1-hr immobilization stress. In contrast, morphine, 6 mg/kg, significantly attenuated struggling, defecation, vocalization and weight loss, and these morphine actions were antagonized by 5 mg/kg of naloxone. These results further support our hypothesis indicating that endogenous opioids released during stress might act to attenuate stress-induced increases in NA turnover in specific brain regions via regionally different subtypes of opiate receptors and that these actions of opioids might be related to the relief of distress-evoked hyperemotional ity in animals.