Drug Dependence and Addiction, II: Adult Neurogenesis and Drug Abuse

The neurobiology of addiction is traditionally thought to involve the “reward pathway” of the brain: the ventral midbrain, nucleus accumbens, and frontal cortex. However, another brain region—the hippocampus—has received renewed interest for its potential role in the initiation, maintenance, and treatment of addiction. Part of this attention is due to the fact that drugs of abuse are potent negative regulators of a striking aspect of the hippocampus: adult neurogenesis.

In the middle of last century, it was discovered that the mammalian brain can give rise to new neurons throughout adulthood. Every species of mammal examined to date—including humans—has been found to have “adult neurogenesis” in just a few discrete brain regions, including the hippocampal dentate gyrus. Adult-generated cells in the dentate gyrus have been shown to mature into hippocampal granule neurons. Of interest is that new neurons in the adult hippocampus have been proposed to be a novel participant in neuroplasticity, or the ability of the adult brain to adapt to new information and new environments.

Chronic administration of drugs of abuse as diverse as opiates, THC, and ethanol decrease hippocampal function as well as decrease the number of new cells born in the dentate gyrus. The drug-induced decrease in adult hippocampal neurogenesis also appears to require chronic administration, since acute administration does not decrease the number of new cells in the dentate gyrus. Given that all drugs of abuse examined to date decrease adult neurogenesis, it has been proposed that an understanding of how these drugs decrease adult hippocampal neurogenesis may help guide the development of treatment strategies for addiction.

Every dividing cell in the body goes through the “cell cycle,” which consists of four phases. Each phase of the cell cycle can be identified with biochemical markers. Traditionally, detection of adult neurogenesis relied on exogenous markers of the S phase, or DNA synthesis phase, of the cell cycle to label and track the birth of new cells. However, a new approach to adult neurogenesis is to use biochemical markers naturally expressed by cells throughout cell division. For example, chronic morphine induces abnormally early division of dividing cells in the mouse dentate gyrus (see Figure), which may block the growth of new neurons in the hippocampus.