Dr. Castañeda investigates plasticity in presynaptic mechanisms that modulate neurotransmitter release during changes in behavior due to neurodegeneration or substance abuse. It is interesting to speculate how fundamental mechanisms that govern learning and memory might serve for compensation in surviving dopamine neurons of the brain compromised by Parkinson’s disease and how these same mechanisms might play a role in the sensitization of dopamine neurons by repeated exposure to stimulant drugs.
Current Research Update: “My research interests involve plasticity of dopamine function during compensation due to neurodegeneration in a rodent model of Parkinson’s disease (PD) and as aberrations in dopamine release that mediate the incessant craving in stimulant drug addiction. I am interested in the presynaptic mechanisms that mediate altered levels of release. In both models of PD and addiction, there is an increase in dopamine release, believed to increase levels, from surviving neurons, that would otherwise be attenuated as dopamine neurons die in the progression of PD and in addiction that might reflect an incentive sensitization for drug craving. Therefore, understanding how mechanisms that regulate release might lead to insights that can further bolster increased release in the degenerative process of PD and, in the contrary, to decrease release that is aberrantly high and may be driving the wanting of drug.”
How IMHR Helped Facilitate This Work: “The IMHR supported parametric studies that allowed me to establish electrical stimulation that evokes dopamine release akin to endogenous neurotransmission and rotational behavior. These parametric studies provided converging evidence that the evoked behavior is regulated by the evoked dopamine release. More importantly, the data suggest that both the evoked dopamine release and behavior are sensitive to blocking action potentials and calcium signaling, both biomarkers for neurotransmission. Both the dopamine release and behavior are evoked in an intensity- and frequency-dependent manner, indicating the activation of neurophysiologically relevant mechanisms that mediate these events. In further research, I have been able to show that electrically evoked dopamine release and rotational behavior show augmented levels of activation in rodents with a history of amphetamine administration that reflects a model of addiction compared to rodents with no history of drug exposure. These results are significant because they suggest potential mechanisms to target for the development of pharmacotherapeutic interventions for stimulant drug addiction.
“It is also important to note that I served as PI on a NIH/NIDA-funded 5-year training grant (2011-2016), the UTEP Vulnerability Issues in Drug Abuse (VIDA) Project. This was a multidisciplinary team of faculty members from five different departments (Psychology, Biology, Linguistics, Public Health Science, Criminal Justice) that derive from three different Colleges (Liberal Arts, Science, Health Sciences). Although it was a team effort across 11 faculty, I credit the AZ IMHR for bestowing me with the competitive edge to successful procure this funding, as I served as the PI.”