Orbitofrontal and insular cortex: neural responses to cocaine-associated cues and cocaine self-administration.
Synapse. 2010-01-01; 64(1): 1-13
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1. Synapse. 2010 Jan;64(1):1-13. doi: 10.1002/syn.20698.
Orbitofrontal and insular cortex: neural responses to cocaine-associated cues and
Guillem K(1), Kravitz AV, Moorman DE, Peoples LL.
(1)Department of Psychiatry, TRL, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, USA.
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.
PMID: 19725114 [Indexed for MEDLINE]