The effects of acute and chronic administration of morphine on norepinephrine turnover in rat brain regions

Abstract

The effects of acute and chronic administration of morphine on norepinephrine turnover in rat brain regions were assessed by measuring changes in the levels of 3-methoxy-4-hydroxyphenyl-glycol sulfate (MHPG-SO 4), the major metabolite of norepinephrine (NE) in rat brain. Acute administration of morphine sulfate (25 mg/kg, i.p.) significantly increased levels of MHPG-SO 4 in hypothalamus, cerebellum, brainstem and “rest of brain” but not in cortex or corpus striatum. After chronic administration of increasing doses of morphine, tolerance developed to this effect of morphine on MHPG-SO 4 levels in cerebellum, brainstem and “rest of brain”, but tolerance to the morphine-induced increase in MHPG-SO 4 levels was not observed in hypothalamus. Sixteen hr after the cessation of chronic morphine administration, levels of MHPG-SO 4 were significantly reduced in hypothalamus. cerebellum and “rest of brain”. These findings are discussed in relation to the regional specificity of the action of morphine on NE turnover, and the possible role of noradrenergic neurons in the reinforcing properties of morphine.