title: Persistent cocaine-induced reversal learning deficits are associated with altered limbic cortico-striatal local field potential synchronization.
abstract: Repeated exposure to cocaine is known to produce persistent deficits in behavioral flexibility. Evidence suggests that these deficits are mediated in part by a circuit involving the medial prefrontal and orbitofrontal cortices (PFC and OFC), nucleus accumbens (NAC), and basolateral amygdala (BLA). To assess the effects of cocaine on this circuit, we treated rats with cocaine daily for 14 d, followed by 4 weeks of abstinence. Animals were then tested on a cross-maze-based reversal learning and set-shifting task, after which they were anesthetized to allow for recording of spontaneous local field potential (LFP) activity simultaneously from all four regions, in addition to activity evoked from acute BLA stimulation. Cocaine-treated (COC) animals showed specific deficits in reversal learning; furthermore, spontaneous LFP oscillation power was reduced and BLA-induced oscillation power was increased in all regions compared with saline-treated (SAL) rats. Theta-burst stimulation of BLA potentiated BLA-evoked responses in all regions and cocaine challenge reduced spontaneous oscillation power and evoked response amplitude, with no COC/SAL group differences. Notably, cocaine challenge produced differential changes in coherence between OFC-BLA, BLA-NAC, and OFC-NAC in COC and SAL groups. These data indicate that repeated exposure to cocaine can produce changes in oscillatory LFP synchronization along limbic cortico-striatal circuits that persist long into abstinence. Furthermore, the regional specificity of these changes strongly correlates with the observed behavioral deficits. Aberrant synchronization within and between regions and consequent dysregulation of the neurocircuitry involved in executive control may contribute to the long-lasting maladaptive decision making seen in cocaine abusers.
authors.affiliation: Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
authors.forename: Clinton B
authors.initials: CB
authors.lastname: McCracken
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
mesh_terms: D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008032:Limbic System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects* / Q000502:physiology; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology
chemical_list: D003042:Cocaine