title: The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity.
abstract: The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Colon-Perez
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Tran
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Khalil
authors.initials: K
authors.lastname: Thompson
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Pace
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Blum
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.|William R Maples Center for Forensic Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Goldberger
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gold
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.|Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Adriaan W
authors.initials: AW
authors.lastname: Bruijnzeel
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.|Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Setlow
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.|Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.|Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D015198:Designer Drugs / Q000008:administration & dosage; D018492:Dopamine Antagonists / Q000008:administration & dosage; D005475:Flupenthixol / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D020318:Rats, Long-Evans; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D015198:Designer Drugs; D018492:Dopamine Antagonists; D011619:Psychotropic Drugs; D011759:Pyrrolidines; D005475:Flupenthixol; D000094982:Synthetic Cathinone