TY - JOUR
T1 - Functional connectivity of chronic cocaine use reveals progressive neuroadaptations in neocortical, striatal, and limbic networks
AU - Orsini, Caitlin A.
AU - Colon-Perez, Luis M.
AU - Heshmati, Sara C.
AU - Setlow, Barry
AU - Febo, Marcelo
N1 - Funding Information:
This work was supported in part by National Institutes of Health Grants DA-038009 (M.F.), DA-024671 (B.S.), and DA-036534 (B.S.); a McKnight Brain Institute Postdoctoral Fellowship (L.M.C.-P.); a Thomas H. Maren Postdoctoral Fellowship (C.A.O.); and the National High Magnetic Field Laboratory Advanced Magnetic Resonance Imaging & Spectroscopy (AMRIS) Facility (National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies.
Publisher Copyright:
© 2018 Orsini et al.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Brain imaging studies indicate that chronic cocaine users display altered functional connectivity between prefrontal cortical, thalamic, striatal, and limbic regions; however, the use of cross-sectional designs in these studies precludes measuring baseline brain activity prior to cocaine use. Animal studies can circumvent this limitation by comparing functional connectivity between baseline and various time points after chronic cocaine use. In the present study, adult male Long–Evans rats were trained to self-administer cocaine intravenously for 6 h sessions daily over 14 consecutive days. Two additional groups serving as controls underwent sucrose self-administration or exposure to the test chambers alone. Functional magnetic resonance imaging was conducted before self-administration and after 1 and 14 d of abstinence (1d and 14d Abs). After 1d Abs from cocaine, there were increased clustering coefficients in brain areas involved in reward seeking, learning, memory, and autonomic and affective processing, including amygdala, hypothalamus, striatum, hippocampus, and thalamus. Similar changes in clustering coefficient after 1d Abs from sucrose were evident in predominantly thalamic brain regions. Notably, there were no changes in strength of functional connectivity at 1 or 14 d after either cocaine or sucrose self-administration. The results suggest that cocaine and sucrose can change the arrangement of functional connectivity of brain regions involved in cognition and emotion, but that these changes dissipate across the early stages of abstinence. The study also emphasizes the importance of including baseline measures in longitudinal functional neuroimaging designs seeking to assess functional connectivity in the context of substance use.
AB - Brain imaging studies indicate that chronic cocaine users display altered functional connectivity between prefrontal cortical, thalamic, striatal, and limbic regions; however, the use of cross-sectional designs in these studies precludes measuring baseline brain activity prior to cocaine use. Animal studies can circumvent this limitation by comparing functional connectivity between baseline and various time points after chronic cocaine use. In the present study, adult male Long–Evans rats were trained to self-administer cocaine intravenously for 6 h sessions daily over 14 consecutive days. Two additional groups serving as controls underwent sucrose self-administration or exposure to the test chambers alone. Functional magnetic resonance imaging was conducted before self-administration and after 1 and 14 d of abstinence (1d and 14d Abs). After 1d Abs from cocaine, there were increased clustering coefficients in brain areas involved in reward seeking, learning, memory, and autonomic and affective processing, including amygdala, hypothalamus, striatum, hippocampus, and thalamus. Similar changes in clustering coefficient after 1d Abs from sucrose were evident in predominantly thalamic brain regions. Notably, there were no changes in strength of functional connectivity at 1 or 14 d after either cocaine or sucrose self-administration. The results suggest that cocaine and sucrose can change the arrangement of functional connectivity of brain regions involved in cognition and emotion, but that these changes dissipate across the early stages of abstinence. The study also emphasizes the importance of including baseline measures in longitudinal functional neuroimaging designs seeking to assess functional connectivity in the context of substance use.
KW - Cocaine
KW - Functional connectivity
KW - Network analysis
KW - Rat
KW - Resting-state fMRI
KW - Self-administration
UR - http://www.scopus.com/inward/record.url?scp=85052133778&partnerID=8YFLogxK
U2 - 10.1523/ENEURO.0081-18.2018
DO - 10.1523/ENEURO.0081-18.2018
M3 - Article
C2 - 30073194
AN - SCOPUS:85052133778
SN - 2373-2822
VL - 5
JO - eNeuro
JF - eNeuro
IS - 4
M1 - e0081-18.2018
ER -