Rats were given daily trials to determine relative preference for an opiate (etonitazene, ETZ) or for water. Animals with a greater history of previous drug exposure developed ETZ preferences more rapidly than did relatively drug-naive animals. Pretreatment with adequate blocking doses of naloxone reduced drug intake to near zero in most subjects. However, animals with the greatest history of prior addiction continued to drink large quantities of ETZ, despite pretreatment with relatively large doses of naloxone. These results can be explained by assuming that stimuli associated with the reinforcing properties of the opioid solution become strong conditioned reinforcers, capable of maintaining responding for long periods of time despite blockade of the reinforcement properties of the drug.
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