Morphine administered post-trial can induce potent conditioned morphine effects

Abstract

Morphine has substantial pro-dopamine effects and in rodents, this is expressed in behavior as increased locomotor activation. Here we administered post-trial 3 dose levels of morphine (3.0, 5.0 and 10.0 mg/kg) or vehicle either immediately or after a 15 min delay to different groups of rats following a brief (5 min) exposure to a novel test environment. Three post-trial injections were administered on three successive days. One day after the first post-trial morphine injections, the non-drug activity levels in the immediate post-trial morphine treatment groups were selectively increased compared to vehicle groups. The activity effects were potentiated with repeated immediate post-trial morphine treatments but the same morphine treatments given after a 15 min post-trial delay did not increase activity in any tests and did not differ from vehicle. Subsequently, all groups were given 5 daily non-drug test sessions as an extinction protocol. The increased activity levels in the 5.0 and 10.0 mg/kg immediate post-trial morphine groups were sustained over the five extinction sessions. Two days later all groups were given a 30 min non-drug test and the 5.0 and 10.0 immediate post-trial groups continued to exhibit a heightened level of activity relative to vehicle restricted to the initial 10 min of the test session. There were no other group differences. The findings that the locomotor stimulant effects in the immediate post-test morphine groups occurred on non-drug tests and that the same morphine treatments given 15 min post-test were without effect are consistent with a conditioned morphine effect. In that acquisition of familiarization with a new environment is a basic learning process that engages consolidation mechanisms, it is possible that the immediate post-trial morphine effects that occur concurrently with consolidation can become incorporated into this consolidation process and subsequently be expressed as a conditioned drug effect.

Keywords: Conditioning; Extinction; Locomotor activity; Memory consolidation; Morphine; Novel environment.