Dependence on one substance tended to decrease the probability of remission from dependence on another substance. Chronic substance users may have difficulty overcoming the effect of drug-associated environmental cues and associative learning related to their drug-seeking behavior [51, 52]. Vulnerability to relapse and drug use maintenance have been also associated with the development of molecular adaptations resulting from chronic drug use, including the elevation of the GluR1 glutamate receptor subunit in the ventral tegmental area, alterations in the content and function of proteins such as the tyrosine hydroxylase, dopamine transporters, RGS9-2, and D2 autoreceptors and the D1-receptor- mediated stimulation of ΔFosB, a transcriptional regulator that modulates the synthesis of certain AMPA glutamate receptor subunits and cell-signaling enzymes [53, 54]. The existence of shared molecular pathways as well as the potential of certain drugs of abuse to induce cross-tolerance and cross-sensitization to one another can also contribute to the lower probability of remission among individuals with dependence on other drugs [55]. Genetic studies also suggest a significant overlap across substances in the genetic liability to dependence. For example, nicotine and alcohol
