Escalation of cocaine intake and incubation of cocaine seeking are correlated with dissociable neuronal processes in different accumbens subregions.
Biological Psychiatry. 2014-07-01; 76(1): 31-39
DOI: 10.1016/j.biopsych.2013.08.032
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1. Biol Psychiatry. 2014 Jul 1;76(1):31-9. doi: 10.1016/j.biopsych.2013.08.032. Epub
2013 Oct 9.
Escalation of cocaine intake and incubation of cocaine seeking are correlated
with dissociable neuronal processes in different accumbens subregions.
Guillem K(1), Ahmed SH(2), Peoples LL(3).
Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, Unité Mixte
de Recherche 5293, Bordeaux, France; Centre National de la Recherche
Scientifique, Institut des Maladies Neurodégénératives, Unité Mixte de Recherche
5293, Bordeaux, France. Electronic address: .
(2)Université de Bordeaux, Institut des Maladies Neurodégénératives, Unité Mixte
de Recherche 5293, Bordeaux, France; Centre National de la Recherche
Scientifique, Institut des Maladies Neurodégénératives, Unité Mixte de Recherche
5293, Bordeaux, France.
(3)Department of Pharmacology and Physiology, Drexel University College of
Medicine, Philadelphia, Pennsylvania.
BACKGROUND: Cocaine addiction is characterized by a progressive increase in drug
intake and a persistent craving for the drug during prolonged abstinence. Whether
these two prominent features of cocaine addiction are related to each other and
are mediated by similar or different neuronal processes is currently unknown.
METHODS: Rats were first allowed to self-administer cocaine under long-access
(6-hour) conditions to induce escalation of cocaine intake. Self-administration
sessions were designed to measure both drug seeking and drug taking. After
escalation, rats underwent a 1-month period of forced abstinence after which they
were re-exposed to cocaine to induce re-escalation of cocaine intake. In vivo
electrophysiologic recordings were conducted in the core and shell subregions of
the nucleus accumbens (NAc) during cocaine intake escalation, after abstinence
and during re-escalation.
RESULTS: After abstinence, escalated levels of cocaine taking decreased toward
pre-escalation levels, whereas cocaine seeking increased persistently. These
opposite postabstinence changes were uncorrelated. At the neuronal level, the
postabstinence decrease in cocaine taking was correlated with a normalization of
depressed neuronal activity in the NAc shell that had developed during escalation
of cocaine intake. In contrast, the incubation-like increase in cocaine seeking
was selectively correlated with a persistent increase in the proportion of
neurons in the NAc core that phasically fire during cocaine seeking.
CONCLUSIONS: These findings show that cocaine taking and cocaine seeking evolve
differently during abstinence from extended drug use and depend on dissociable
neuronal processes in different subregions of the nucleus accumbens.
© 2013 Society of Biological Psychiatry Published by Society of Biological
Psychiatry All rights reserved.
DOI: 10.1016/j.biopsych.2013.08.032
PMID: 24120118 [Indexed for MEDLINE]