Orbitofrontal and insular cortex: neural responses to cocaine-associated cues and cocaine self-administration

Synapse. 2010 Jan;64(1):1-13. doi: 10.1002/syn.20698.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / physiopathology*
  • Conditioning, Operant / physiology
  • Cues*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Electrophysiology
  • Male
  • Neurons / drug effects
  • Neurons / physiology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiopathology
  • Rats
  • Rats, Long-Evans
  • Reinforcement Schedule

Substances

  • Dopamine Uptake Inhibitors
  • Cocaine