The neurobiology of cocaine addiction

Abstract

Cocaine produces its psychoactive and addictive effects primarily by acting on the brain's limbic system, a set of interconnected regions that regulate pleasure and motivation. An initial, short-term effect -- a buildup of the neurochemical dopamine -- gives rise to euphoria and a desire to take the drug again. Researchers are seeking to understand how cocaine's many longer term effects produce addiction's persistent cravings and risk of relapse. In the author's laboratory, work has focused on buildup of the genetic transcription factor DeltaFosB. Levels of DeltaFosB in the limbic system correlate with addiction-like behaviors in mice and may precipitate very long-lasting changes to nerve cell structure. Further pursuit of this and similar leads are first steps toward a complete understanding of the transition from cocaine abuse to addiction -- and, ultimately, more effective treatments for those who are addicted.

FROM THE RUSH TO THE ADDICTION, COCAINE'S EFFECTS IN THE BRAIN

(Brain inset) Cocaine causes euphoria in the short term and addiction in the long term via its effects on the brain’s limbic system, which consists of numerous regions, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), centers for pleasure and feelings of reward; the amygdala and hippocampus, centers for memory; and the frontal cortex, a center for weighing options and restraint. (Main panel) Cocaine causes the neurotransmitter dopamine to build up at the interface between VTA cells and NAc cells, triggering pleasurable feelings and NAc cellular activities that sensitize the brain to future exposures to the drug. Among the activities are increased production of genetic transcription factors, including ΔFosB; altered gene activity; altered production of potentially many proteins; and sprouting of new dendrites and dendritic spines. (Graph inset) The time courses of cocaine-induced buildup of ΔFosB and cocaine-related structural changes (dendrite sprouting) suggest that these neurobiological effects may underlie some of the drug’s short-term, medium-term, and long-term behavioral effects.