Functional Connectivity of Chronic Cocaine Use Reveals Progressive Neuroadaptations in Neocortical, Striatal, and Limbic Networks

eNeuro. 2018 Jul 24;5(4):ENEURO.0081-18.2018. doi: 10.1523/ENEURO.0081-18.2018. eCollection 2018 Jul-Aug.


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.

Keywords: cocaine; functional connectivity; network analysis; rat; resting-state fMRI; self-administration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / diagnostic imaging
  • Cocaine-Related Disorders / physiopathology*
  • Connectome / methods
  • Corpus Striatum* / diagnostic imaging
  • Corpus Striatum* / drug effects
  • Corpus Striatum* / physiopathology
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology*
  • Limbic System* / diagnostic imaging
  • Limbic System* / drug effects
  • Limbic System* / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Neocortex* / diagnostic imaging
  • Neocortex* / drug effects
  • Neocortex* / physiopathology
  • Nerve Net* / diagnostic imaging
  • Nerve Net* / drug effects
  • Nerve Net* / physiopathology
  • Rats
  • Rats, Long-Evans
  • Self Administration
  • Sucrose / administration & dosage
  • Sucrose / pharmacology*
  • Sweetening Agents / administration & dosage
  • Sweetening Agents / pharmacology*


  • Dopamine Uptake Inhibitors
  • Sweetening Agents
  • Sucrose
  • Cocaine