Integrating behavioral and molecular approaches in mouse: Self-administration studies

Drug addiction is a serious mental illness involving severe motivational disturbances and a loss of behavioral control leading to personal devastation. The behavioral symptoms that accompany drug addiction can be modeled in rodents based on changes in their drug self-administration behavior. These symptoms include compulsive and escalating amounts of drug intake, along with a propensity for drug-seeking behavior in withdrawal, reflecting aberrations in the neural substrates that regulate these behaviors. Animal drug self-administration studies attempt to link neurobiological changes with the manifestation of specific behavioral symptoms. Since most changes in neuronal function stem from molecular “neuroadaptations” that occur in specific cell types in anatomically discrete brain regions, modern technological advances can be used to manipulate single gene targets with similar anatomical precision, and at postdevelopmental stages of adulthood, in order to mimic the neuroadaptations produced by chronic drug use. This approach is necessary to delineate important functional interactions that underlie the etiology of primary disease symptoms.