Evidence of possible opiate dependence during the behavioral depressant action of a single dose of morphine

Rats were trained to lever press for food pellets under a 20 response fixed ratio (FR 20) schedule of reinforcement. A single injection of 15 mg morphine SO₄/kg suppressed operant behavior for $\text{1}\text{1}\text{2}\text{–3}\text{1}\text{2}\text{hrs}$, after which time responding resumed at a reduced rate. When 0.25 mg naloxone HCl/kg was given during the recovery phase, the behavioral depressant effect of the narcotic was immediately reversed and operant performance returned to predrug rates. In contrast, when 0.5 mg naloxone/kg was given at this time, operant behavior was abolished for at least 1 hr. Naloxone, at these doses, did not affect responding in drug-naive subjects. These results suggest that a single, relatively low dose of morphine can induce transient dependence which is detectable for several hrs after drug administration, at a time when the acute pharmacological actions of morphine are still apparent.