title: Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens.
abstract: Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n = 12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed 'phasically active') relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n = 12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the 'brain reward system' following abstinence and resumption (relapse) of cocaine consumption.
authors.affiliation: Department of Psychology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Hollander
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carelli
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine