This project wants to contribute to generate new therapeutic targets for the treatment of cocaine addiction (...). We will study: 1- What histaminergic receptors (H\sub 1\nosub, H\sub 2\nosub H\sub 3\nosub ) modulate cocaine seeking by rats. 2- What brain region may mediate those effects. 3- The colocalization of histaminergic and dopaminergic receptors in the nucleus accumbens and with tyrosine hydroxylase in the ventral tegmental area, brain regions forming part of the mesolimbic dopamine system. 4- How histaminergic receptors can influence the transduction mechanisms of dopaminergic receptors, specifically, the control of dopamine synthesis and release by D\sub 2\nosub receptors and of CREB phosphorylation by D\sub 1\nosub receptors. 5- What enduring changes take place in the brains of abstinent rats that contribute to explain cocaine craving. Our hypothesis postulates that H\sub 3\nosub receptors agonists (perhaps together with other histaminergic agonists) would modulate the dopaminergic-GABAergic output in the nucleus accumbens, and therefore they may become a new therapeutic target for drug addiction treatment.