Abstract
The acute administration of morphine resulted in an increase in the levels of the sulfate conjugate of 3-methoxy-4-hydroxyphenylglycol (MHPG-SO 4), a major metabolite of norepinephrine in rat brain. Pretreatment with naloxone, at doses which did not significantly alter MHPG-SO 4, attenuated the morphine-induced increase in MHPG-SO 4. The morphine-induced increase in levels of MHPG-SO 4 was not the result of a drug-induced blockade of the egress of the metabolite from brain, since the rate of disappearance of MHPG-SO 4 in animals pretreated with pargyline was similar in morphine-treated and control groups. Moreover, morphine did not inhibit the uptake of intracisternally administered 1-norepinephrine-H 3 nor did it produce alterations in norepinephrine-H 3 metabolism. With chronic administration of morphine, tolerance developed to the morphine-induced increase in MHPG-SO 3 levels in rat brain, and, following cessation of chronic treatment with morphine, the levels of MHPG-SO 4 were significantly decreased.
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