An intraventricular infusion model for inducing morphine dependence in rats: quantitative assessment of precipitated withdrawal.

An experimental model of morphine dependence, in which rats were made dependent upon morphine by intraventricular infusion, is described. Morphine dependence was assessed and quantified by a series of withdrawal signs that were induced by the intraperitoneal administration of the morphine antagonist naloxone. The infusion of different concentrations of morphine resulted in the production of physical dependence, the severity of which was directly correlated with the concentration of morphine infused. A weak to moderate degree of dependence characterized by such withdrawal signs as teeth chattering, whole-body shakes, and vocalization was produced by infusions of morphine less than 5 micrograms/hr. A strong degree of physical dependence characterized by additional dominant withdrawal signs such as jumping and launching was produced by the infusion of 50 micrograms/hr morphine. The morphine pellet model that most closely approximated this degree of dependence was a three-pellet model in which a single 75-mg morphine pellet was implanted at 48-hr intervals. Abstinence precipitated by removal of the morphine-containing osmotic minipumps was characterized primarily by teeth chattering and whole-body shakes which persisted for at least 48 hr.