The Impact of Opioids and Opiates on Adult Hippocampal Neurogenesis
Harburg, Gwyndolen Colleen
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Opiate addiction is a growing problem in today's society. Thus, it is of crucial importance that we understand the physiological basis for opiate addiction and the long-term consequences of opiate use in order to develop more effective means of treatment. Chronic morphine and heroin have previously been shown to decrease proliferation and survival of progenitor cells in the adult rat and mouse hippocampus. Here, I show that endogenous opioids may act through the mu opioid receptor (MOR) to similarly decrease survival of new hippocampal neurons. An exon 1 MOR knockout mouse showed increased survival of new neurons independent of effects on cell proliferation or cell death. In concordance with the increased numbers of granule cells maturing into neurons, knockout mice also had larger hippocampal granule cells layers and increased numbers of granule cells. Exploration of the impact of chronic morphine on different stages of neurogenesis showed that chronic morphine decreased numbers of Type 1 stem cells and proliferating progenitor cells. Progenitor cells exposed to chronic morphine during early maturation were not significantly decreased in number, but appeared to have retarded cell maturation since fewer had reached the immature neuron stage in chronic morphine mice. Chronic morphine also appeared to result in anterior hippocampus specific decreases in stem cells as well as maturation retardation. These findings show that morphine has distinct effects on different stages of neurogenesis, and that the anterior hippocampus may be more sensitive to some effects. Cell proliferation levels in the brains of human heroin abusers and normal controls were assessed using the endogenous proliferation marker Ki67. Heroin abusers had decreased numbers, but larger clusters of proliferating cells in the dentate gyrus hilus as compared with controls. There was also a trend towards a decrease in number of proliferating cells in the granule cell layer of heroin abusers. Although these findings are preliminary, they suggest that chronic heroin use in humans, as in rodents, may negatively impact neurogenesis. Together, these findings support a negative role for opioids and opiates in regulating adult hippocampal neurogenesis.