Influence of cocaine self-administration on learning related to prefrontal cortex or hippocampus functioning in rats.
BACKGROUND
Individuals who abuse cocaine have cognitive deficits, particularly in functions associated with the orbitofrontal cortex. It is not clear to what extent the impact of cocaine on cognitive functioning is related to its role as a behavioral reinforcer. A preclinical means to investigate this issue is to use a yoked-triad procedure in which sets of three animals either contingently self-administer cocaine or receive passive administration of cocaine or saline in a noncontingent manner.


OBJECTIVE
Using this procedure, we assessed cocaine's effect on learning that requires a functionally intact prefrontal cortex (prelimbic or insular/orbital subregions) or hippocampus.


METHODS
Rats self-administering 1-mg/kg unit doses of cocaine responded under a fixed-ratio 5, time-out 20-s schedule of drug delivery. Testing took place in a radial-arm maze within the first 30 min after 2-hr drug sessions ended, beginning after 2.5 months of cocaine or saline exposure.


RESULTS
Rats self-administering cocaine earned 14-18 infusions on average throughout different phases of the study. In groupwise comparisons, learning in the visually guided delayed win-shift (prelimbic prefrontal cortex-related) and win-shift (hippocampus-related) tasks was not influenced by contingent or noncontingent cocaine exposure. Session latency, though, was shorter in both cocaine-exposed groups during the win-shift task. During the odor-guided delayed win-shift task (insular/orbital prefrontal cortex-related), learning was disrupted in rats self-administering cocaine, with no influence of noncontingent cocaine exposure.


CONCLUSIONS
Based on these and previous findings, learning related to functioning of the insular/orbital prefrontal cortex and amygdala is the most consistently disrupted in cocaine-intoxicated rats after long-term drug exposure.
Kantak
Kathleen M
KM
Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University, MA 02215, USA. kkantak@bu.edu
Udo
Tomoko
T
Ugalde
Francisco
F
Luzzo
Christopher
C
Di Pietro
Nina
N
Eichenbaum
Howard B
HB
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration / Q000379:methods
D003042:Cocaine