Genetic basis of drug dependence and comorbid behavioral traits

Drug dependence is characterized by symptoms causing uncontrollable use of a drug despite its negative consequences. Dependence occurs only in a small fraction of individuals who try an addictive drug, and there is a large variance in individual susceptibility to dependence. Individuals susceptible to dependence exhibit specific comorbid behavioral traits, such as sensation seeking, novelty seeking, and antisocial personality. Studies using genetically engineered mice have delineated the extent to which various genes contribute to both dependence susceptibility and comorbid behavioral traits. Evidence suggests that the genes for dopamine D4 receptor, phosphodiesterease1B, the AMPA receptor subunit GluR1, 5HT1B receptor, protein kinase C and the transcription factor FosB contribute to both dependence susceptibility and comorbid behavioral traits. However, MAO-B influences a behavioral response to novelty without affecting nicotine dependence susceptibility. The mechanisms by which genes influence dependence susceptibility and comorbid behavioral traits are likely to be complex.