Orbitofrontal and Insular Cortex: Neural Responses to Cocaine-Associated Cues and Cocaine Self-Administration

Department of Psychiatry, TRL, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Synapse (Impact Factor: 2.13). 01/2010; 64(1):1-13. DOI: 10.1002/syn.20698
Source: PubMed


Based on neuro-imaging studies in cocaine-addicted humans, it is hypothesized that increases in neural activity within several regions of the prefrontal cortex contribute to cue-induced cocaine seeking and cocaine-induced compulsive drug self-administration. However, electrophysiological tests of these hypotheses are lacking. In the present study, animals were trained to self-administer cocaine (0.75 mg/kg) for 14 days. On the 14th day, we conducted electrophysiological recordings of lateral orbitofrontal (LO) and ventral anterior insula (AIV) neurons. A subset of the combined population of recorded neurons showed a change in firing rate in association with one or more of the following discrete events: (1) presentation of a discriminative stimulus that signaled the onset of the self-administration session, (2) occurrence of the first cocaine-directed operant response, (3) occurrence of a cocaine-reinforced press, and (4) presentation of cues normally paired with delivery of the cocaine reinforcer. The majority of the stimulus- and response-related changes in firing involved a brief increase in firing during the stimulus and response event, respectively. In addition to these event-specific responses, approximately half of the recorded neurons exhibited a sustained change in average firing (i.e., discharges per 30-s bin) during the cocaine self-administration session, relative to average firing during a presession, drug-free period (referred to as session changes). The prevalence of session-increases and decreases were not significantly different. These and other findings are discussed in relation to hypotheses about cue-evoked and cocaine-maintained cocaine-directed behavior.

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    • "Many of these neurons are activated only by cues that were previously associated with one reward (cocaine) but not by another reward (food) (Carelli and Ijames, 2001; Carelli, 2002b) which suggests that reward-associated cues or contexts are also encoded in distinct ensembles. Similar types of drug-and cue-induced phasic firing have been observed in different areas of the prefrontal cortex (Chang et al., 1997a; Chang et al., 1997b; Chang et al., 1998; Chang et al., 2000; Guillem et al., 2010; West et al., 2014). Overall, these studies support the hypothesis that distinct neuronal ensembles encode different learned associations underlying drug-and non-drug related behaviors. "
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