Continuous administration of opioids produces locomotor sensitization

Sensitization, a behavioral phenomenon characterized by an escalating pattern of drug response following repeated administration, is thought to be involved in the development of addiction. Research on certain drugs of abuse, most notably the psychomotor stimulants amphetamine and cocaine, suggests that two factors are important to the development of sensitization: (1) drugs must be administered intermittently, rather than continuously, and (2) drugs must be administered in association with specific environmental cues. The present studies were performed to determine if the same requirements exist for opioid sensitization. If sensitization occurs following continuous infusion of the drugs, then neither intermittent administration nor specific environmental cues can be critical. Morphine was administered continuously with pellets (2 x 75 mg) or osmotic pumps (20 mg/kg/day), and fentanyl was administered continuously with osmotic pumps (0.2 mg/kg/day) to male Sprague-Dawley rats. Continuous infusion of either morphine or fentanyl led to an escalating pattern of activity that is characteristic of sensitization to the locomotor effects of the drugs. The escalation of activity was evident across different measures of activity, and persisted beyond continuous administration. The results suggest that, unlike sensitization to cocaine or amphetamine, intermittent administration and environmental specificity are not critical to opioid sensitization. These findings may have implications for the treatment of pain and addiction.