Persistence of relapse of morphine-seeking behavior in rats: the relative role of certain biological variables.

The theory that narcotic-induced protracted biological changes are responsible for relapse of opiate-reinforced behavior was examined in the rat. Groups of rats were conditioned to prefer a distinctive environment by pairing it with morphine doses from 1-200 mg/kg, and were retested for persistence of this preference after a 3-week abstinence period. They were then observed for protracted signs such as sensitivity to naloxone, tolerance to morphine analgesia, hyperaggression, or changes in endocrine activity. Acquisition and relapse of the preference, as well as long-term tolerance, were dose related. None of the purported protracted signs showed any consistent relationship to the tendency to relapse. However, relapse correlated significantly with original acquisition scores in all relapsing groups. The results suggest that original conditioning factors, rather than protracted changes, are responsible for the observed relapse.