title: Functional connectivity in frontal-striatal brain networks and cocaine self-administration in female rhesus monkeys.
abstract: BACKGROUND
  Cocaine addiction is characterized by alternating cycles of abstinence and relapse and loss of control of drug use despite severe negative life consequences associated with its abuse.
  
  
  OBJECTIVE
  The objective of the present study was to elucidate critical neural circuits involved in individual vulnerabilities to resumption of cocaine self-administration following prolonged abstinence.
  
  
  METHODS
  The subjects were three female rhesus monkeys in prolonged abstinence following a long history of cocaine self-administration. Initial experiments examined the effects of acute cocaine administration (0.3 mg/kg, IV) on functional brain connectivity across the whole brain and in specific brain networks related to behavioral control using functional magnetic resonance imaging in fully conscious subjects. Subsequently, these subjects were allowed to resume cocaine self-administration to determine whether loss of basal connectivity within specific brain networks predicted the magnitude of resumption of cocaine intake following prolonged abstinence.
  
  
  RESULTS
  Acute cocaine administration robustly decreased global functional connectivity and selectively impaired top-down prefrontal circuits that control behavior, while sparing connectivity of striatal areas within limbic circuits. Importantly, impaired connectivity between prefrontal and striatal areas during abstinence predicted cocaine intake when these subjects were provided renewed access to cocaine.
  
  
  CONCLUSIONS
  Based on these findings, loss of prefrontal to striatal functional connectivity may be a critical mechanism underlying the negative downward spiral of cycles of abstinence and relapse that characterizes cocaine addiction.
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Murnane
authors.forename: K S
authors.initials: KS
authors.lastname: Gopinath
authors.forename: E
authors.initials: E
authors.lastname: Maltbie
authors.forename: J B
authors.initials: JB
authors.lastname: Daunais
authors.forename: Q K
authors.initials: QK
authors.lastname: Telesford
authors.forename: L L
authors.initials: LL
authors.lastname: Howell
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D005260:Female; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D009434:Neural Pathways / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology; D012646:Self Administration; D012737:Sex Factors; D013375:Substance Withdrawal Syndrome / Q000473:pathology
chemical_list: D003042:Cocaine