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Extended‐access and yoked‐access to cocaine self‐administration have distinct behavioral and molecular profiles.
Author(s) -
Ploense Kyle Lawrence,
Vieira Philip,
Kippin Tod E.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.561.7
Subject(s) - self administration , saline , free access , drug intoxication , addiction , anesthesia , medicine , psychology , neuroscience , world wide web , computer science
Cocaine addiction is a chronic disorder that involves escalation of intake over time. Both humans and rodents will self‐administer escalating doses of cocaine when the drug is readily available. However, when cocaine access is restricted, escalation of intake is not apparent in rodents. Here, we investigated escalation of cocaine intake and active lever responding in rats as a function of control over intake. Rats were implanted with a permanent jugular catheter and then allowed to lever press to self‐administer (FR1, 20s time‐out with a 20s light cue paired with each infusion) saline vehicle (0.1 ml/infusion) cocaine (0.25 mg/infusion) under 4 conditions: limited‐access (1 h/ day) to saline, limited‐access to cocaine, extended‐access (6 h/day) to cocaine condition, and limited‐access + yoked‐access (1h/day + 5 h/day, respectively) to cocaine. Based on the first 10 min and first hour of daily access, we observed rapid escalation of cocaine intake in both the extended‐access and limited‐access + yoked conditions (ps < 0.05). We also observed a delayed escalation of cocaine intake in the limited‐access condition within the first 10 min of self‐administration (p < 0.05), but not within the first 1 h of self‐administration. Interestingly, escalation of cocaine intake in the limited access + yoked‐access rats was much faster than in the extended access rats. However, relative to the other cocaine conditions, the limited‐access + yoked group exhibited markedly less efficient self‐administration (i.e. more non‐reinforced relative to reinforced lever responses) during both the first 10 min and 1 h of daily self‐administration (ps<0.05). Additionally, post‐mortem quantification of homer2 (a gene implicated in cocaine cued learning) mRNA expression within the dmPFC indicated elevation only in the extended‐access conditions (p<0.05). Together, these findings indicate that either contingent or non‐contingent “excessive” cocaine exposure supports escalation but has distinct effects on the temporal patterning of operant responsiveness as well as molecular correlates of escalation. Support or Funding Information NARSAD NIH (R21DA027115) Keck Award