Short early manipulations of rodent postnatal environment may trigger long-term effects on neurobiological and behavioural phenotypes in adulthood. However, little is known about such effects of handling on the vulnerability to develop drug dependence. The present study aimed to analyze the long-term effects of a brief handling (1 min) on morphine and ethanol dependence and on the preproenkephalin (PPE) mRNA and μ opioid receptor levels. Handled rats showed a significant increase in morphine (25 mg/l) but not ethanol (10%) consumption and preference after 7 weeks and no difference in morphine (2 and 5 mg/kg) conditioned place preference. No difference of preproenkephalin mRNA and μ opioid receptor levels was detected in the mesolimbic system between both groups. These data emphasize that human brief handling, which can lead to morphine dependence development, constitutes in itself an experimental treatment and not a control condition.