Vulnerability to the development of drug-intake has been studied by using the acquisition of intravenous amphetamine self-administration in the rat. In a series of neurobiological experiments we provoked imbalances in the functioning of the dopaminergic (DA) network by performing lesions of the DA cell bodies in the ventral tegmental area, DA terminals in the amygdala or median raphe nucleus. These imbalances which resulted in enhanced DA transmission ratio between the nucleus accumbens and the prefrontal cortex led to an increase in the rapidity of self-administration acquisition. With a psychobiological approach, we showed that individual differences in vulnerability to develop self-administration in rats of the same strain were correlated with locomotor responses to stress and to an acute injection of amphetamine. Moreover, activation of DA transmission by repeated amphetamine injections changed animals resistant to drug-intake into vulnerable ones. It is suggested that some inherited or acquired factors, at least in part by affecting the activity of DA network, can predispose individuals to drug abuse.