Sensitization to the motor effects of contingent infusions of heroin but not of kappa agonist RU 51599.

It has been postulated that behavioral sensitization could reflect drug-induced changes that are central to the development of drug abuse; however, it is still unknown whether behavioral sensitization can arise during a "voluntary" and "self-controlled" consumption of drugs and consequently play a role in drug abuse. For this reason, we studied the possible sensitization of motor activity during ten consecutive intravenous self-administration (SA) sessions of one of the most largely abused opiates the mu agonist heroin [30 microg/infusion (inf)]. We also studied in similar conditions the new kappa agonist RU 51599 (6.5, 20 and 100 microg/inf). Heroin and RU 51599 were compared because both drugs are self-administered by rodents, but the reinforcing properties of RU 51599 are very weak compared to those of heroin. At low ratio requirement rats developed SA of both heroin and RU 51599; however, a progressive increase in drug-induced locomotor activity over subsequent sessions was observed only for heroin but not for RU 51599. Sensitization of the motor effects of heroin developed over a period of time during which the intake of the drug was constant. In conclusion, sensitization can develop during the voluntary consumption of an addictive drug such as heroin. These results are in line with the hypothesis that sensitization could play a role in the etiology of drug abuse.