Parametric evaluation of the development of sensitization to the effects of morphine on locomotor activity.

Animals repeatedly administered drugs of abuse often become more sensitive to their effects. It has been proposed that this behavioral sensitization may serve as a useful model for changes that may underlie the etiology and maintenance of drug-seeking behavior. This study was designed to determine systematically some of the conditions of drug exposure under which sensitization occurs to morphine-induced stimulation of locomotor activity. Groups of rats (n=8 per group) were exposed to a regimen of intermittent morphine or saline injections for 1--4 days and tested at later time points with morphine or saline. The amount of behavioral sensitization observed was related to the number of drug exposures, but not to the dose of morphine used during drug exposures. Sensitization to morphine persisted for as long as 3 months and was completely blocked when naltrexone was administered with the test dose of morphine after the final morphine exposure. Administration of naltrexone with morphine during the exposure regimen did not alter the development of behavioral sensitization. These results indicate a robust behavioral sensitization to morphine that appears to be influenced in an orderly manner within a narrow window of the drug exposure conditions.