Orbitofrontal and insular cortex: neural responses to cocaine-associated cues and cocaine self-administration.
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.
Guillem
Karine
K
Department of Psychiatry, TRL, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Kravitz
Alexxai V
AV
Moorman
David E
DE
Peoples
Laura L
LL
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000502:physiology; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine