Sensitivity to the narcotic cue in non-dependent, morphine-dependent and post-dependent rats

Using a food-reinforced two-lever operant procedure, 12 rats were trained to discriminate 10 mg/kg (i.p.) of morphine from saline. Five animals were given daily non-contingent exposure to morphine (20 mg/kg on saline, or no-test days, and 10 mg/kg on drug days) from the beginning of the experiment; the others received injections of saline. In the morphine generalization tests, the dependent rats showed an increased sensitivity to the narcotic cue as compared with non-dependent animals (ratio of the ED50 values: 2.30). This increased sensitivity was still present 3 months after discontinuing the non-contingent treatment with morphine (ratio of the ED50 values: 1.98). The results of the present study, together with other results reported in the literature, suggest that the experimental procedure plays a role in determining whether tolerance, no tolerance or enhanced sensitivity to the discriminative stimulus properties of narcotics, is observed.