A persistent opioid-addiction state of memory.

We determined whether tolerance develops to a morphine-induced state of memory. Rats were injected with 5 mg/kg of morphine and trained to complete a FR-10 schedule of lever presses in daily sessions. The dose-response curve of morphine (1.25-40 mg/kg) in enabling retrieval was tested in one group immediately after criterion had been reached and, in another group, after an additional 40 training sessions. The additional training enhanced, rather than attenuated, the dependence of retrieval on morphine; this was because the further gain in response latency that developed during additional training also became state-dependent. Thus, because tolerance did not develop to the morphine state, an increasingly large body of engrams became encoded in that state, rendering retrieval increasingly dependent.