The neurobiology of addiction is an elaborate combination of genetic predisposition, environmental influence, and behavioral patterns which are in many cases critically difficult to break. A three-step neurobiological approach can best help us understand the neural and genetic substrates underlying addiction.
Animal models demonstrate that changes in circuitry of the mesolimbic pathway in particular are susceptible to changes which in many cases are irreversible and thus impact behavior long-term. Glutamatergic feedback pathway disruption and disturbances to the nigrostriatal pathways also play a part in relapse behavior.
In animals, many manipulations of reward and punishment reveal the underpinnings of addiction which are comparable to how we see addiction in humans. Depriving addicted animals of their drug gives us information about which behaviors are stimulated when an animal is deprived. Manipulations of anatomy, access to resources, and even environmental changes can significantly change addiction patterns and compensatory behaviors.
Both PET and fMRI studies can help us visualize the structures responsible for addictive behavior, with strong evidence that the amygdala, ventral striatum, orbitofrontal cortex and dorsal striatum are all implicated as significant. Genetic analyses of potential regions of the genome responsible for addiction are discussed in several models, with alpha-synuclein a strong contender at the time of publication for a gene implicated in addiction across various studies.