School of Biomedical Sciences

Funding

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National Institutes of Health, National Institute on Drug Abuse (NIDA K25DA047458)

Funding Nida LogTitle: Determining the effects of bath salts on cognitive control and functional brain connectivity

Abstract: Abstract “Bath salts” or synthetic cathinones drugs potential of chronic use, ability to alter behaviors like cognitive control and alterations in the brain makes them a significant healthcare concern. One of the most harmful bath salts is 3,4-methylenedioxypyrovalerone (MDPV). The adverse behavioral effects of MDPV can last days-to- to weeks, possibly due to alteration in dopamine neurotransmissions. Research into drug has shown that MDPV is similar pharmacologically to cocaine but longer-lasting. However, an essential unexplored aspect of MDPV is how it alters cognitive control and whether changed cognitive control underlies some of the most severe behavioral outcomes of MDPV use. Cognitive control refers to a set of mental processes driving the organization and mediation of goal-oriented behavior. In this grant, two specific cognitive control domains of interest are flexibility and impulsivity. These two subprocesses are compromised in substance use disorders and can lead to uncontrolled drug-seeking behavior. Using fMRI, we recently showed that after 24 hours, an acute MDPV administration in rats caused an increase in brain connectivity, specifically in frontal cortical regions such as orbitofrontal (OrF), infralimbic (IL), prelimbic (PL), and subcortical reward regions including striatum, amygdala, and nucleus accumbens (NAc). These changes in connectivity could underlie some of the most dangerous effects of MDPV by inducing long-lasting changes in the connectivity of cognitive control brain circuitry. Therefore, we hypothesize that sustained self-administration of MDPV will increase functional connectivity between the frontal cortex (PL, IL, and OrF), thalamus, amygdala, and NAc leading to impairments in cognitive control functions. We will test this hypothesis using rodents trained to chronically self-administer MDPV for ten days. The proposed research addresses gaps in our understanding of how MDPV undermines cognitive control and which brain regions are most affected and calculates connectivity changes in the brain with fMRI. This project will assess two cognitive control, impulsivity, and flexibility subprocesses.

Brain Behavior Research Foundation, NARSAD Young Investigator Grant

Funding Bbrf LogTitle: Longitudinal biophysical markers of neuroinflammation due to morphine self-administration. 

Abstract: Researchers increasingly recognize that neuroinflammation is an important feature in mental health disorders and illnesses. Generating in vivo markers of neuroinflammation will be a valuable clinical tool to improve clinical tracking of mental health disorders. This work’s goal is to further our understanding of substance abuse disorders (SUD) and addiction by developing and validating novel and sensitive neuroinflammatory in vivo markers predictive of these disorders. Given MRI translational applicability, the results can easily be integrated into human studies of SUDs; however, careful study using animal models will provide the quantitative relationship between the exact timing of the neuroinflammatory response and observable changes in the MRI indices of microstructural integrity. Given the widespread link between neuroinflammation and mental health disorders, the results of this study can also provide clues to better understand other neuropsychiatric disorders. The completion of the proposed studies will lead to advances in developing early clinical MRI markers of SUDs and their temporal relationship to the neuroinflammatory process.