Chronic morphine administration: plasma levels and withdrawal syndrome in rats.

Morphine, administered to Sprague-Dawley rats over a period of 65 hr either by the simultaneous implantation of two 75 mg pellets, or by a series of twice daily 20 or 30 mg/kg injections, produced dependence as indicated by the precipitation of the abstinence syndrome with the antagonist, naloxone. Plasma morphine levels, analyzed fluorometrically at various times during the treatment procedures, revealed peak concentrations that were 3 or 4 fold higher for injected animals than the maximum steady-state level established in the pellet-implanted animals. The calculated plasma concentration of the drug over time was not statistically different for the groups. It is noted that although the 2 methods of morphine administration produce a qualitatively identical dependent state, the pellet implantation technique causes greater weight loss and a higher incidence of jumping and wet-dog shakes during withdrawal.