The Role of the Hippocampus in Cocaine Responses

Experiences generate sensory information that is processed in the cortex then transmitted through the hippocampus, where memories of these experiences are formed, consolidated, and modified. The hippocampus is critical for drug–environment associations, which can underlie relapse to abuse, and control of the mesolimbic dopamine circuitry, which mediates the rewarding effects of the drug. Cocaine regulates hippocampal activity in human addicts and animal models of addiction, and long-term exposure to cocaine changes molecular, structural, and functional properties of hippocampal neurons. Of particular interest are changes in the molecules underlying synaptic plasticity (i.e., long-term potentiation), and associated changes in hippocampal synapse number and strength that accompany exposure to and withdrawal from cocaine. Emerging data indicate that cocaine-driven changes in hippocampal synaptic function, neuronal birth, and projections to other regions may drive key aspects of addiction, and manipulations of these pathways may represent important targets for future therapeutic intervention in cocaine addiction.