THE EFFECT OF 6-HYDROXYDOPAMINE ON MORPHINE TOLERANCE AND PHYSICAL DEPENDENCE

¹ Department of Pharmacology, School of Medicine, University of California, San Francisco, California

The effect of 6-hydroxydopamine (6-OHDA), which is known to deplete selectively catecholamines by destruction of catecholaminergic neurons, was investigated in mice rendered tolerant to and dependent upon morphine by pellet implantation. Pretreatment with 6-OHDA intracerebrally with a dose that caused 66 and 30% depletion of norepinephrine and dopamine, respectively, reduced the analgetic response of morphine (AD50) in both tolerant and nontolerant mice without modifying the brain uptake of morphine. The relative increase in morphine AD50 in both groups was approximately the same, and it was concluded that 6-OHDA affects the acute response to morphine but not the process primarily involved in initiating the development of tolerance to morphine. Precipitated abstinence, as measured by naloxone-induced withdrawal jumping was enhanced by 6-OHDA pretreatment; weight loss after abrupt withdrawal was also increased by 6-OHDA. The possibility that catecholamines may be involved in the stereotyped withdrawal jumping behavior observed in morphine-dependent mice is suggested.

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