Patterns of functional activity associated with cocaine self-administration in the rat change over time.
BACKGROUND
Although imaging studies in human addicts have been valuable for identifying the neural substrates of the effects of abused drugs, few studies have used this approach in animal models where conditions can be carefully controlled.


OBJECTIVE
To define the substrates that mediate the effects of cocaine in a rodent model of cocaine self-administration using the 2-[(14)C]deoxyglucose method and to assess changes in these patterns over the course of drug exposure.


METHODS
Male Sprague-Dawley rats self-administered cocaine (0.75 mg/kg per injection; FR2; 21 injections/session) and control rats received saline infusions in the same pattern as the cocaine rats for 5 or 30 days. Metabolic mapping was applied immediately after the final session.


RESULTS
Following 5 days of self-administration, rates of glucose utilization were decreased in the nucleus accumbens, and increased in autonomic brainstem structures and in sensorimotor regions. After 30 days of cocaine exposure, self-administration reduced glucose utilization throughout the dorsal and ventral striatum, central nucleus of the amygdala, medial forebrain bundle, and infralimbic and prelimbic prefrontal cortices. In addition, at this time point glucose utilization was no longer elevated in any autonomic or sensorimotor brain regions.


CONCLUSIONS
These data demonstrate that the distribution of functional activity associated with self-administered cocaine undergoes considerable change over the course of drug exposure. While increases in metabolic rates were largely found in autonomic and sensorimotor structures after short-term cocaine access, decreases were prominent in mesocorticolimbic regions after prolonged exposure. These differences in the patterns of brain activity that develop with long-term cocaine self-administration may play a role in the transition to habitual drug seeking behavior.
Macey
Darrel J
DJ
Department of Physiology and Pharmacology, Center for the Neurobiological Investigation of Drug Abuse, Wake Forest University School of Medicine, Winston Salem, NC 27157-1083, USA.
Rice
Wendy N
WN
Freedland
Cory S
CS
Whitlow
Christopher T
CT
Porrino
Linda J
LJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
D001786:Blood Glucose; D000697:Central Nervous System Stimulants; D003847:Deoxyglucose; D003042:Cocaine