Effects of self-administered cocaine in adolescent and adult male rats on orbitofrontal cortex-related neurocognitive functioning.
BACKGROUND
Deficits in amygdala-related stimulus-reward learning are produced following 18 drug-free days of cocaine self-administration or its passive delivery in rats exposed during adulthood. No deficits in stimulus-reward learning are produced by cocaine exposure initiated during adolescence.


OBJECTIVE
To determine if age of initiating cocaine exposure differentially affects behavioral functioning of an additional memory system linked to cocaine addiction, the orbitofrontal cortex.


METHODS
A yoked-triad design (n = 8) was used. One rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling drug delivery (1.0 mg/kg) self-administered cocaine from either P37-P59 or P77-P99, and then underwent 18 drug-free days (P60-P77 vs. P100-P117). Rats next were tested for acquisition of odor-delayed win-shift behavior conducted over 15 sessions (P78-P96 vs. P118-P136).


RESULTS
Cocaine self-administration did not differ between adults and adolescents. During the test phase of the odor-delayed win-shift task (relatively difficult task demands), rats from both drug-onset ages showed learning deficits. Rats with cocaine self-administration experience committed more errors and had longer session latencies compared to rats passively receiving saline or cocaine. Rats with adolescent-onset cocaine self-administration experience showed an additional learning deficit by requiring more sessions to reach criterion levels for task acquisition compared to same-aged passive saline controls or rats with adult-onset cocaine self-administration experience. Rats passively receiving cocaine did not differ from the passive saline control from either age group.


CONCLUSIONS
Rats with adolescent-onset cocaine self-administration experience were more impaired in an orbitofrontal cortex-related learning task than rats with adult-onset cocaine self-administration experience.
Harvey
Roxann C
RC
Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University, 64 Cummington Street, Boston, MA, 02215, USA.
Dembro
Kimberly A
KA
Rajagopalan
Kiran
K
Mutebi
Michael M
MM
Kantak
Kathleen M
KM
D000367:Age Factors; D000818:Animals; D016739:Behavior, Addictive; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine