Morphine administered post-trial induces potent morphine conditioned effects if the context is novel but not if the context is familiar.

Morphine administered shortly after exposure to a novel environment induces potent locomotor stimulant conditioning. Environmental novelty is important as pre-exposure (PE) to a stimulus can attenuate the capacity to acquire conditioned stimulus (CS). Here, the importance of environmental novelty for the efficacy of an open-field to become a CS for elicitation of a morphine conditioned response was assessed by comparing the effects of morphine administered post-trial following a 5 min exposure to a novel environment versus a PE environment. Four groups of rats (2 vehicle and 2 morphine groups) were used. Two groups received ten daily 5 min non-drug PEs to an open-field arena and the other two groups were not pre-exposed to the environment. Subsequently, all groups received post-trial injections of either vehicle or morphine immediately after each of five daily 5 min sessions in the open-field. Importantly, on the first day of testing prior to the first post-test morphine administration, the locomotor activity of the novel and PE groups was not different. Over the 5 post-trial morphine treatments, the activity of the PE morphine group, the PE vehicle and the novel environment vehicle groups did not change and were equivalent. In contrast, in the novel environment morphine group, a conditioned hyper-activity response increased with repeated post-trial morphine treatments. For the morphine group it is suggested that the novel environment initiated a post-trial stimulus trace that occurred in temporal contiguity with the post-trial drug response and enabled the trace to become a CS for the morphine unconditioned response. In contrast, PE induced a latent inhibition effect in the PE morphine group, thus the post-trial CS trace was insufficient to become associated to the morphine response and no conditioning occurred. In addition to conventional drug induced Pavlovian delay conditioning, the findings are suggestive of drug induced Pavlovian trace conditioning.