Parametric evaluation of the development of sensitization to the effects of morphine an locomotor activity

Animals repeatedly administered drugs of abuse often become more sensitive to their effects. It has been proposed that this behavioral sensitization m ay serve as a useful model for changes that may underlie the etiology and m aintenance of drug-seeking behavior. This study was designed to determine s ystematically some of the conditions of drug exposure under which sensitiza tion occurs to morphine-induced stimulation of locomotor activity. Groups o f 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 mor phine or saline. The amount of behavioral sensitization observed was relate d to the number of drug exposures, but nut to the dose of morphine used Jur ing drug exposures. Sensitization to morphine persisted for as long as 3 mo nths and was completely blocked when naltrexone was administered with the t est dose of morphine after the final morphine exposure. Administration of n altrexone with morphine during the exposure regimen did not alter the devel opment of behavioral sensitization. These results indicate a robust behavio ral sensitization to morphine that appears to be influenced in an orderly m anner within a narrow window of the drug exposure conditions. (C) 2001 Else vier Science Ireland Ltd. All rights reserved.