Research Overview
Drug-induced neuroplasticity of reward and pain pathways of the central nervous system.
1. Drug addiction is characterized by a progressive increase in drug intake despite negative consequences. This strong and consistent behavior in addicted individuals suggests a maladaptive change in both the motivational and reward systems of the brain. Glutamate derived strengthening of specific neuronal pathways after repeated activation is a well established mechanism of neuronal learning. It appears that a similar change in glutamatergic activation of mesocorticolimbic dopamine neurons occurs following repeated drug administration, resulting in decreasing reward but increased drug seeking and craving. My ongoing research utilizes electron microscopic immunocytochemistry to examine drug-induced (opiates and stimulants) changes in glutamate receptor trafficking within dopaminergic neurons originating in the ventral tegmental area (VTA). Additionally, behavioral measures are assessed to correlate changes in locomotion, nociception, and the subcellular localization of glutamate receptor following repeated drug administration to obtain a more comprehensive understanding of processes leading to the development of addiction.
2. Opiates are the most effective treatment for moderate to severe pain. However, the chronic use of opiates is hampered by the development of tolerance and dependence. These conditions may be driven by an upregulation of pro-nociceptive mechanisms within the descending pain modulatory system. Repeated opiate administration may increase glutamatergic activation of pro-nociceptive neurons within the rostral ventromedial medulla (RVM) leading to a decreased analgesic effect over time. My ongoing research correlates changes in activity of RVM neurons, following repeated morphine administration, to changes in the subcellular localization of glutamatergic and opioid receptors within various structures of the descending pain modulatory system. Further, pro-inflammatory cytokines and chemokines are upregulated by opiates and have been shown to increase pain sensitivity by increasing glial glutamate release. As such, immune activation of the descending system following repeated opiate administration is also being examined.
