Incubation of Cocaine Craving After Intermittent-Access Self-administration: Sex Differences and Estrous Cycle.
Biological Psychiatry. 2019-06-01; 85(11): 915-924
DOI: 10.1016/j.biopsych.2019.01.015
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Nicolas C(1), Russell TI(1), Pierce AF(1), Maldera S(1), Holley A(2), You ZB(3),
McCarthy MM(2), Shaham Y(1), Ikemoto S(4).
Author information:
(1)Behavioral Neuroscience Branch, Intramural Research Program, National
Institute on Drug Abuse, Baltimore, Maryland.
(2)Department of Pharmacology, University of Maryland School of Medicine,
Baltimore, Maryland.
(3)Molecular Targets and Medications Discovery Branch, Intramural Research
Program, National Institute on Drug Abuse, Baltimore, Maryland.
(4)Behavioral Neuroscience Branch, Intramural Research Program, National
Institute on Drug Abuse, Baltimore, Maryland. Electronic address:
.
Comment in
Biol Psychiatry. 2019 Jun 1;85(11):e53-e54. doi:
10.1016/j.biopsych.2019.04.006.
BACKGROUND: Studies using continuous-access drug self-administration showed that
cocaine seeking increases during abstinence (incubation of cocaine craving).
Recently, studies using intermittent-access self-administration showed increased
motivation to self-administer and seek cocaine. We examined whether intermittent
cocaine self-administration would potentiate incubation of craving in male and
female rats and examined the estrous cycle’s role in this incubation.
METHODS: In experiment 1, male and female rats self-administered cocaine either
continuously (8 hours/day) or intermittently (5 minutes ON, 25 minutes OFF × 16)
for 12 days, followed by relapse tests after 2 or 29 days. In experiments 2 and
3, female rats self-administered cocaine intermittently for six, 12, or 18
sessions. In experiment 4, female rats self-administered cocaine continuously
followed by relapse tests after 2 or 29 days. In experiments 3 and 4, the
estrous cycle was measured using a vaginal smear test.
RESULTS: Incubation of cocaine craving was observed in both sexes after either
intermittent or continuous drug self-administration. Independent of access
condition and abstinence day, cocaine seeking was higher in female rats than in
male rats. In both sexes, cocaine seeking on both abstinence days was higher
after intermittent drug access than after continuous drug access. In female
rats, incubation of craving after either intermittent or continuous drug access
was significantly higher during estrus than during non-estrus; for intermittent
drug access, this effect was independent of the training duration.
CONCLUSIONS: In both sexes, intermittent cocaine access caused time-independent
increases in drug seeking during abstinence. In female rats, the time-dependent
increase in drug seeking (incubation) is critically dependent on the estrous
cycle phase.
Published by Elsevier Inc.
DOI: 10.1016/j.biopsych.2019.01.015
PMCID: PMC6534474
PMID: 30846301 [Indexed for MEDLINE]
Conflict of interest statement: Financial Disclosures The authors report no
biomedical financial interests or potential conflicts of interest.