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

Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St, HSF-2 S251, Baltimore, MD 21201, USA.
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


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.


Available from: Geoffrey Schoenbaum, Feb 03, 2014
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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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    ABSTRACT: Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis. This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment. We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes. Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward. These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.
    Psychopharmacology 08/2013; 229(3). DOI:10.1007/s00213-013-3222-6 · 3.88 Impact Factor
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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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    ABSTRACT: We revisit our hypothesis that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntarily drug use to habitual, and ultimately compulsive drug use. We especially focus on the transitions in striatal control over drug seeking behaviour that underlie these transitions since functional heterogeneity of the striatum was a key area of Ann Kelley's research interests and one in which she made enormous contributions. We also discuss the hypothesis in light of recent data that the emergence of a compulsive drug seeking habit both reflects a shift to dorsal striatal control over behaviour and impaired prefontal cortical inhibitory control mechanisms. We further discuss aspects of the vulnerability to compulsive drug use and in particular the impact of impulsivity. In writing this review we acknowledge the untimely death of an outstanding scientist and a dear personal friend.
    Neuroscience & Biobehavioral Reviews 02/2013; 37(9). DOI:10.1016/j.neubiorev.2013.02.010 · 8.80 Impact Factor
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    • "Several studies have shown that neuronal activity in the OFC encodes certainty about reward estimation [31] [33] [34]. In rats, the OFC has been described as having an important role in discounting value tasks [77], while reversal learning deficits are associated with the inability of OFC neurons to specifically develop response-outcome associations before and after the preferred choice is made [59] [66]. "
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    ABSTRACT: It has been recently described that disruption of the neural mechanisms of emotion-based decision making occurs in both chronic pain patients and in animal models of pain; moreover, it also has been shown that chronic pain causes morphological and functional changes in the prefrontal cortex that may be crucial for this decision-making dysfunction. However, it is not known whether pain alone is capable of altering the neuronal encoding of decision exhibited by prefrontal neurons. We have previously shown that naïve animals have risk-averse performance in the rodent gambling task, whereas chronic pain animals reverse their choice preference and become risk prone. Using this paradigm, we chronically implanted arrays of multielectrodes and recorded from neuronal ensembles in the orbitofrontal cortex of freely moving animals performing 4 sessions of the rodent gambling task: 2 in control conditions and 2 after the onset of inflammatory pain induced by complete Freund's adjuvant injection. Our results show that the instantaneous neuronal firing rate was correlated with the probability of choosing a specific lever in 62.5% of the neurons; however, although in the control sessions 61% of the neurons encoded the reward magnitude, after the pain onset only 16% of the neurons differentiated small from large rewards. Moreover, we found that the fraction of risk-sensitive neurons recorded in each session predicted the overall risk bias of the animal. Our data suggest that orbitofrontal cortex encoding of risk preference is compromised in chronic pain animals.
    Pain 05/2012; 153(8):1625-35. DOI:10.1016/j.pain.2012.04.011 · 5.21 Impact Factor
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