TY - JOUR
T1 - The psychoactive designer drug and bath salt constituent MDPV causes widespread disruption of brain functional connectivity
AU - Colon-Perez, Luis M.
AU - Tran, Kelvin
AU - Thompson, Khalil
AU - Pace, Michael C.
AU - Blum, Kenneth
AU - Goldberger, Bruce A.
AU - Gold, Mark S.
AU - Bruijnzeel, Adriaan W.
AU - Setlow, Barry
AU - Febo, Marcelo
N1 - Funding Information:
KT was supported by University Scholars Program of the University of Florida. We thank the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility for their continued support (National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida).We thank Dr Craig F Ferris and Dr Praveen Kulkarni (Northeastern University, Boston, MA) for their support with the segmented atlas of the rat brain and to Dr Amanda K. Welch for editorial assistance. This work was funded by National Institute on Drug Abuse Grant R21 DA038009 to MF.
Publisher Copyright:
© 2016 American College of Neuropsychopharmacology.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84963533720&partnerID=8YFLogxK
U2 - 10.1038/npp.2016.40
DO - 10.1038/npp.2016.40
M3 - Article
C2 - 26997298
AN - SCOPUS:84963533720
SN - 0893-133X
VL - 41
SP - 2352
EP - 2365
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 9
ER -