Differential effects of morphine on noradrenaline release in brain regions of stressed and non-stressed rats

Effects of morphine on noradrenaline (NA) turnover in the 8 brain regions were investigated in non-stressed and stressed rats. Morphine at 3 mg/kg and 6 mg/kg caused dose-dependent increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of brain NA, in the hypothalamus, amygdala, thalamus, hippocampus and midbrain and decreases in NA levels in the first 4 of these regions. In contrast to these enhancing effects of morphine on NA release in non-stressed rats, pretreatment with morphine at 6 mg/kg significantly attenuated immobilization-stress-induced increases in MHPG-SO4 levels in the above regions. The morphine effects in both states, non-stressed and stressed, were reversed by naloxone at 0.5 mg/kg and 5 mg/kg in the hypothalamus, amygdala and thalamus. These neurochemical changes are apparently related to the distress-evoked hyperemotionality. Behavioral changes observed during the restraint stress such as struggling, vocalization and defecation were attenuated by morphine at 6 mg/kg and enhanced by naloxone at 5 mg/kg, and this action of morphine was also reversed by naloxone at 5 mg/kg. These results suggest that morphine acts to attenuate stress-induced increases in NA release in the hypothalamus, amygdala and thalamus via opiate receptors, although the drug facilitates NA release in these regions in non-stressed rats. Together with previous findings that naloxone enhances stress-induced increases in NA release selectively in these regions, it is further suggested that endogenous opioids released during stress might act to inhibit NA release in these specific brain areas and that these decreased noradrenergic activities might be closely related to the relief of the distress-evoked hyperemotionality in animals.