A rapid assessment of stimulus properties of morphine

The difficulty in assessing stimulus properties of drugs becomes apparent when the test drug, like morphine, carries both aversive and reinforcing effects at certain doses. Mice (ICR Crj strain) were trained in a passive avoidance conditioning using a two-compartment shuttle-box. On alternate days, morphine (3.0 mg/kg) was paired with shock in one compartment and saline with shock in the other compartment. A total of 3 morphine/saline pairings were given. Animals were then tested 7 times, one test per day, with saline and different doses of morphine (0.75, 1.12, 1.32, 0.93, 1.50, 3.0 mg/kg) to reveal the stimulus properties of morphine. The preference for the morphine-conditioned safe compartment after morphine injections was used to indicate that the animals associated some "stimulus" or "motivational" properties of morphine with the cues of the safe compartment. The animals discriminated very well between saline and low doses of morphine on the one hand, and higher doses of morphine (close to that given during conditioning) on the other. The discontinuity between injections responded to as saline and those responded to as morphine was virtually complete between 1.12 and 1.32 mg/kg of morphine. These findings demonstrate that the present method can be used to establish an association between some stimulus properties of morphine and avoidance of shock. Accordingly, the successful discrimination of the animals between the two compartments revealed some stimulus properties of morphine.