The Role of Adult Hippocampal Neurogenesis in Morphine Addiction
The hippocampus plays a large role in modulating the reward pathway, being especially important in craving and context-dependent relapse. One form a neuroplasticity within the hippocampus is adult neurogenesis, which occurs in the subgranular zone of the dentate gyrus. While a growing amount of literature has explored the effects of drugs of abuse on adult DG neurogenesis, the relationship between self-administered opiates and adult DG neurogenesis remains unexplored. This dissertation investigates both the role of adult DG neurogenesis in morphine-related behaviors and the effects of self-administered opiates (morphine and heroin) on adult DG neurogenesis. I first explore the background literature important in the work completed within this dissertation (Chapter 1). Next, using a self-administration paradigm, I proceed to show that ablation of adult neurogenesis via cranial irradiation results in increased in morphine intake, decreased extinction, and decreased cognitive flexibility. Additionally, rats lacking adult DG neurogenesis exhibited increased morphine locomotor sensitization with increased DG activation in the infrablade after a low dose morphine challenge (Chapter 2). I will then go on to investigate the consequences of long-term self-administered opiates (morphine and heroin) on the different stages of maturation of adult-generated neurons. I demonstrate that morphine self-administration has no effect on proliferation, survival, or maturation immediately after exposure or after 28 days of withdrawal (Chapter 3). Additionally, I demonstrate that heroin self-administration does not alter DCX+ cell density or granule cell layer volume (Chapter 4). Taken together, my data suggests the adult DG neurogenesis is robust and normally unaffected by self-administered opiates. However, preexisting deficits in DG neurogenesis may lead to an increased vulnerability to addiction-related behaviors. In the final chapter (Chapter 5), I discuss potential implications of this work and future directions in which it may be taken.
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