Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for addiction and stem cell biology

Abstract

Once thought to produce global, nonspecific brain injury, drugs of abuse are now known to produce selective neuro-adaptations in particular brain regions. These neuro-adaptations are being closely examined for clues to the development, maintenance, and treatment of addiction. The hippocampus is an area of particular interest, as it is central to many aspects of the addictive process, including relapse to drug taking. A recently appreciated hippocampal neuro-adaptation produced by drugs as diverse as opiates and psychostimulants is decreased neurogenesis in the sub-granular zone (SGZ). While the role of adult-generated neurons is not clear, their functional integration into hippocampal circuitry raises the possibility that decreased adult SGZ neurogenesis may alter hippocampal function in such a way as to maintain addictive behavior or contribute to relapse. Here, we review the impact of opiates and psychostimulants on the different stages of cell development in the adult brain, as well as the different stages of the addictive process. We discuss how examination of drug-induced alterations of adult neurogenesis advances our understanding of the complex mechanisms by which opiates and psychostimulants affect brain function while also opening avenues for novel ways of assessing the functional role of adult-generated neurons. In addition, we highlight key discrepancies in the field and underscore the necessity to move "beyond BrdU"--beyond merely counting new hippocampal cells labeled with the S phase marker bromodeoxyuridine--so as to probe mechanistic questions about how drug-induced alterations in adult hippocampal neurogenesis occur and what the functional ramifications of alterations in neurogenesis are for addiction.