Our primary research focus is to investigate the neurophysiological changes that occur with chronic exposure to drugs of abuse. I am specifically interested in aberrant drug induced neuroadaptations in brain dopamine systems that are linked to impaired cognition, mood and social interactions. These are often reported with chronic psychostimulant abuse and the development of psychosis. Such behavioral adaptations have been observed to entail reductions in functional connectivity between areas of the brain mediating cognitive function (prefrontal cortex) and reward (mesolimbic dopamine areas). We have recently found that chronic exposure to a potent synthetic drug present in bath salt formulations causes disruption of functional connectivity between prefrontal areas and dorsal striatum. Furthermore, we have recent evidence suggesting that the effects of this drug on functional connectivity and behavior may involve an altered brain immune response.




Deleterious effects of ‘bath salt’ drugs on brain structure and function: Bath-salt drugs continue to be a national and international concern as new molecular variants of these synthetic psychoactive drugs continue to emerge (at least 77 bath salts now identified worldwide). Modifications to the chemical structure of existing bath salts are done in attempts to evade law enforcement. Thus, studying known bath salts may reveal key behavioral and neurobiological effects shared among various novel variants introduced into the ‘legal high’ market. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) is often detected in blood of patient’s presenting at emergency rooms with a psychosis-like syndrome involving agitation, panic, confusion/cognitive impairment, violent behavior, and depression. The mechanisms underlying MDPV’s behavioral disturbances and its effect on brain network activity and connectivity following its chronic use are unknown. A major objective of our research is to characterize in vivo neuroadaptations caused by repeated use of novel psychoactive cathinone drugs, particularly compounds sharing molecular structure and exerting similar behavioral effects with MDPV. We have conducted studies as part of our NIDA funded R21 (DA038009) to determine the effects of MDPV on social and affective behavior, functional connectivity, and neuroinflammation. Across studies there is general agreement that single exposure to MDPV impacts behavioral measures 24 h later. We have also observed that the effects of a single MDPV injection on functional connectivity can last 24 h. Although we have not yet determined the effects of chronic MDPV on behavior and functional connectivity, we have assessed its chronic effects on neuroinflammation. Overall, our results demonstrate increased neuroinflammation after 5 days of MDPV administration.