Longitudinal Changes in Brain Metabolic Activity after Withdrawal from Escalation of Cocaine Self-Administration.
Neuropsychopharmacol. 2017-05-29; 42(10): 1981-1990
DOI: 10.1038/npp.2017.109
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Nicolas C(1)(2), Tauber C(3), Lepelletier FX(3), Chalon S(3), Belujon P(1)(2),
Galineau L(3), Solinas M(1)(2).
Author information:
(1)INSERM, U1084, Poitiers, France.
(2)Université de Poitiers, U1084, Poitiers, France.
(3)UMR INSERM U930, Université François Rabelais de Tours, Tours, France.
Comment in
Sci Transl Med. 2017 Jul 5;9(397):eaan8201. doi:
10.1126/scitranslmed.aan8201.
The chronic and relapsing nature of addiction suggests that drugs produce
persistent adaptations in the brain that make individuals with drug addiction
particularly sensitive to drug-related cues and stress and incapable of
controlling drug-seeking and drug-taking behavior. In animal models, several
long-lasting neuroadaptations have been described. However, few studies have
used brain-imaging techniques to provide a complete picture of brain functioning
in the course of withdrawal from cocaine. In this study, we allowed rats to
self-administer cocaine under short-access (1-h/day) or long-access (6-h/day)
conditions and used 2-deoxy-2-(18F)fluoro-d-glucose (18FDG) positron emission
tomography scanning to investigate the longitudinal changes in metabolic
activity 1 and 4 weeks after discontinuation of cocaine self-administration. We
found that compared to naive rats, both long-access and short-access rats showed
significant disruptions in basal brain metabolic activity. However, compared to
short-access, long-access rats showed more intense, and long-lasting
neuroadaptations in a network of brain areas. In particular, abstinence from
extended access to cocaine was associated with decreased metabolic activity in
the anterior cingulate cortex, the insular cortex, and the dorsolateral
striatum, and increased metabolic activity in the mesencephalon, amygdala, and
hippocampus. This pattern is strikingly similar to that described in humans that
has led to the proposal of the Impaired Response Inhibition and Salience
Attribution model of addiction. These results demonstrate that extended access
to cocaine leads to persistent neuroadaptations in brain regions involved in
motivation, salience attribution, memory, stress, and inhibitory control that
may underlie increased risks of relapse.
DOI: 10.1038/npp.2017.109
PMCID: PMC5561337
PMID: 28553833 [Indexed for MEDLINE]