Conditioned withdrawal signs elicited by contextual cues for morphine administration

Pavlovian conditioning theories of drug dependence argue that drugor withdrawal-associated cues elicit motivational conditioned responses that enhance the likelihood or intensity of drugtaking behavior. The present experiment assessed whether drug-associated cues can elicit a con· ditioned withdrawal reaction in rats. In support of previous research, we found clear evidence for conditioned withdrawal. When tested without morphine in a distinctive environment, animals that had received morphine paired with that environment showed more pronounced signs of withdrawal than did animals that had received equivalent doses of morphine unpaired with the test environment. Despite differential levels of withdrawal reactions, consumption ofthe potent opiate etonitazene in the test environment was not influenced by conditioning. Prior morphine experience did increase both the rate of barpressing for and the level of consumption of oral etonitazene compared with saline control levels. Performance in paired animals, however, was not superior to that in unpaired animals. Although clearly demonstrating conditioned withdrawal, these observations question the importance of withdrawal in the acquisition of oral selfadministration of an opiate.