Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.
Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.
Henry
Porche' Kirkland
PK
Division of Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Murnane
Kevin S
KS
Votaw
John R
JR
Howell
Leonard L
LL
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D012055:Reinforcement Schedule; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D019788:Fluorodeoxyglucose F18; D003042:Cocaine; D004298:Dopamine