Conditioned increases in locomotor activity produced with morphine as an unconditioned stimulus, and the relation of conditioning to acute morphine effect and tolerance.

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Abstract
Rats administered 5 mg/kg morphine SO4, through s.c. implanted catheters, during each of several daily sessions in an open field showed a progressive increase in locomotor activity measured in the open field prior to each morphine administration. Since the increases in activity were not observed in rats given morphine in a different environment (home cage) and saline in the open field, it is concluded that the increases were due to conditioning. The increases in activity were retained over a 7 day rest period; they were also produced when a 2nd opiate (5 .mu.g/kg etorphine HCl) was substituted for morphine, were not seen when 2 mg/kg naloxone HCl (i.p.) was administered during treatment and were present in rats showing tolerance to opiate produced hypoactivity. The direct effect of morphine on activity is believed to have a biphasic dose-response curve; thus, the relation of dose to conditioning was also studied. Increases in activity were the only conditioned behaviors observed; they were present only at the higher doses (16, 4 and 1 vs. 0.25, 0.065 and 0 mg/kg) and they occurred whether or not the dose was associated with unconditioned hypoactivity. The discussion deals with the relation of conditioning and morphine tolerance, the question of whether the unconditioned stimulus of morphine conditioning is a compensatory or a direct effect of morphine and the similarity of conditioned increases in activity produced by morphine and by other stimuli that are reinforcing.