title: Prelimbic and infralimbic cortical regions differentially encode cocaine-associated stimuli and cocaine-seeking before and following abstinence.
abstract: Cocaine stimuli often trigger relapse of drug-taking, even following periods of prolonged abstinence. Here, electrophysiological recordings were made in rats (n = 29) to determine how neurons in the prelimbic (PrL) or infralimbic (IL) regions of the medial prefrontal cortex (mPFC) encode cocaine-associated stimuli and cocaine-seeking, and whether this processing is differentially altered after 1 month of cocaine abstinence. After self-administration training, neurons (n = 308) in the mPFC were recorded during a single test session conducted either the next day or 1 month later. Test sessions consisted of three phases during which (i) the tone-houselight stimulus previously paired with cocaine infusion during self-administration was randomly presented by the experimenter, (ii) rats responded on the lever previously associated with cocaine during extinction and (iii) the tone-houselight was presented randomly between cocaine-reinforced responding during resumption of cocaine self-administration. PrL neurons showed enhanced encoding of the cocaine stimulus and drug-seeking behavior (under extinction and self-administration) following 30 days of abstinence. In contrast, although IL neurons encoded cocaine cues and cocaine-seeking, there were no pronounced changes in IL responsiveness following 30 days of abstinence. Importantly, cue-related changes do not represent a generalised stimulus-evoked discharge as PrL and IL neurons in control animals (n = 4) exhibited negligible recruitment by the tone-houselight stimulus. The results support the view that, following abstinence, neural encoding in the PrL but not IL may play a key role in enhanced cocaine-seeking, particularly following re-exposure to cocaine-associated cues.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: West
authors.forename: Michael P
authors.initials: MP
authors.lastname: Saddoris
authors.forename: Erin C
authors.initials: EC
authors.lastname: Kerfoot
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carelli
mesh_terms: D000200:Action Potentials; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003214:Conditioning, Classical; D003463:Cues; D058999:Drug-Seeking Behavior; D005108:Extinction, Psychological; D005793:Generalization, Psychological; D008032:Limbic System / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000502:physiology; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors
chemical_list: D003042:Cocaine
keywords: behavior; craving; electrophysiology; relapse; self-administration