Morphine increases hypothalamic noradrenaline turnover but rather decreases its enhancement induced by stress in rats.

Abstract

By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), we investigated the effects of morphine on hypothalamic noradrenergic neurons in stressed or non-stressed states in male rats. Subcutaneous administration of morphine at 3 mg/kg and 6 mg/kg reduced NA level and elevated MHPG-SO4 level in the hypothalamus in a dose-dependent manner and these effects of morphine were completely abolished by pretreatment with naloxone at 0.5 mg/kg and 5 mg/kg (s.c.). Immobilization stress caused significant reduction of NA and increase in MHPG-SO4 level, and this stress-induced increase in NA turnover was attenuated by pretreatment with 3 mg/kg and 6 mg/kg of morphine. Attenuation of stress-induced enhancement of hypothalamic NA turnover by morphine was almost completely reversed by naloxone at 0.5 mg/kg and 5 mg/kg. These results suggest that morphine produces different effects on hypothalamic noradrenergic neurons, depending on the state of the animal treated, i.e., facilitation in the non-stressed state and inhibition in the stressed state and that these actions occur via opiate receptors. It is further suggested that the hypothalamic opioid peptide system might be partially involved in the stress process by attenuating increased NA turnover by stress in rats.