Article

Abnormal associative encoding in orbitofrontal neurons in cocaine‐experienced rats during decision‐making

Department of Psychiatry, University of Maryland, Baltimore, Baltimore, Maryland, United States
European Journal of Neuroscience (Impact Factor: 3.18). 12/2006; 24(9):2643-53. DOI: 10.1111/j.1460-9568.2006.05128.x
Source: PubMed

ABSTRACT

Recent evidence has linked exposure to addictive drugs to an inability to employ information about adverse consequences, or outcomes, to control behavior. For instance, addicts and drug-experienced animals fail to adapt their behavior to avoid adverse outcomes in gambling and reversal tasks or after changes in the value of expected rewards. These deficits are similar to those caused by damage to the orbitofrontal cortex, suggesting that addictive drugs may cause long-lasting changes in the representation of outcome associations in a circuit that includes the orbitofrontal cortex. Here we test this hypothesis by recording from orbitofrontal neurons in a discrimination task in rats previously exposed to cocaine (30 mg/kg i.p. for 14 days). We found that orbitofrontal neurons recorded in cocaine-experienced rats failed to signal the adverse outcome at the time a decision was made in the task. The loss of this signal was associated with abnormal changes in response latencies on aversive trials. Furthermore, upon reversal of the cue-outcome associations, orbitofrontal neurons in cocaine-treated rats with enduring reversal impairments failed to reverse their cue-selectivity, while orbitofrontal neurons in cocaine-treated rats with normal performance showed an increase in the plasticity of cue-selective firing after reversal. These results provide direct neurophysiological evidence that exposure to cocaine can cause behaviorally relevant changes in the processing of associative information in a circuit that includes the orbitofrontal cortex.

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Available from: Geoffrey Schoenbaum, Feb 03, 2014
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    • "Disruption of frontostriatal interactions in cocaine-dependent individuals may be at the core of the behavioral manifestations of addiction, such as compulsive drug seeking and impaired self-control. Indeed, studies in animals have shown that cocaine exposure causes an inability of the OFC to signal adverse outcomes (Stalnaker et al. 2006), which in association with enhanced dorso-striatal activity leads to rigid patterns of behavior (Caprioli, Lucantonio & Schoenbaum 2014). Thus, the 'hard wired' nature of the observed neural changes could explain the notorious difficulties experienced by addicts to abandon drug use even in the face of serious health and social consequences and the high relapse rate observed in this population. "
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    • "Thus, the only reasonable explanation that accounts for the current results is alterations in model-based processing. While this does not preclude a contribution of stronger habits to other aspects of drug seeking, it is in fact consistent with what we and others have reported, which is that psychostimulants cause rather modest changes in information processing in dorsal striatum (Takahashi et al. 2007) while substantially altering that in orbitofrontal cortex (Homayoun and Moghaddam 2006; Stalnaker et al. 2006). So, what are the implications of these findings for understanding and, more importantly, addressing behavioral issues in addiction? "
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    • "Rats having self-administered and then been withdrawn from cocaine exhibited both increased extinction responding and a marked deficit in reversal learning during withdrawal (Calu et al., 2007). Schoenbaum and colleagues have emphasized both the similarity between OFC lesions and these apparently long-lasting effects of relatively short-term treatment with cocaine, but also showed that the deficit in reversal learning is reflected in a change in the properties of OFC neurons, which do not develop appropriate responses to cues predicting outcomes (Stalnaker et al., 2006). Other considerations implicate the orbitofrontal cortex in compulsivity related to chronic drug abuse. "
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