?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- 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 is designed to address existing gaps in our understanding of how MDPV undermines cognitive control and which brain regions are most affected and calculating connectivity changes in the brain with fMRI. In this project, the candidate will assess two subprocesses of cognitive control, impulsivity, and flexibility. The behavior will be analyzed concerning functional connectivity changes of longitudinal resting state fMRI (rsfMRI) data, and neuronal performance-dependent activity using activity regulated cytoskeletal-associated gene (Arc) mRNA expression in rats. Carrying out the proposed research will permit the candidate to incur in an independent research career integrating longitudinal studies of rsfMRI connectivity, behavioral, and Arc cellular analysis into studies of drug use disorders.
Synthetic cathinones, commonly referred to as 'bath salts,' are drugs that alter the functional connectivity in the brain with a high potential for abuse possibly due to alterations in cognitive control; therefore, new studies are needed to understand the relationship between brain connectivity and behaviors of cognitive control under chronic use of bath salts. Out of all bath salts, 3,4-methylenedioxypyrovalerone (MDPV) is one of the most dangerous inducing behavioral changes in memory, locomotor activity, and social interactions, in addition to changes in brain connectivity with acute administration. In this grant, we set out to determine the alterations in brain connectivity induced by chronic MDPV self-administration employing a longitudinal fMRI study and behavioral assays of cognitive control to further understand the relationship between brain connectivity and the deleterious effects of the drug on cognitive control.
