Cocaine Addiction: Neurobiology and Related Current Research in Pharmacotherapy

In this article, recent research studies in the field of cocaine addiction are reviewed, with an eye toward emergent options for treatment innovation. Particular attention is paid to the neurobiology and specific neurotransmitter and receptor mechanisms involved in cocaine abuse, dependence, and other unique phenomena of addiction such as sensitization, craving, compulsive drug use, and withdrawal. The vicissitudes in the dopamine theory of brain reward mechanisms, dopaminergic effects of cocaine, and emerging roles of GABA, serotonin, glutamate, and nitric oxide in cocaine addiction and its sequelae are discussed. Neuroanatomic findings elicited with imaging studies using PET and functional MRI are summarized. These findings support the role of specific brain regions within the dopaminergic system such as the ventral tegmentum and nucleus accumbens in the induction of the cocaine "high" and craving, respectively. Research approaches to the problem of developing effective pharmacotherapeutic options to render cocaine ineffective and modalities under study, such as dopamine uptake inhibitors and immunotherapy, are also discussed in the context of a variety of practical problems faced by these experimental therapies. Pharmacotherapeutic strategies and new directions in this research, such as the adaptive changes of the opioid system in cocaine addiction, are reviewed. Potential areas for further study are brought forth for further debate and possible clinical evaluation.