Project #12963
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#12963 : Gene expression and its regulation during and after inpatient detoxification of cocaine: a link to relapse?
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Name of Applicant : Romain Icick
Date of application : 10-02-2019
Unit : Integrative Neurobiology of Cholinergic Systems
Location : Lwoff
Phone : 0673111129
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Project context and summary :

Cocaine is the most widely used illicit stimulant in Europe1, with a recent increase in use in the French general population. Cocaine addiction (CocAdd) is recognised as a public health priority worldwide, affecting 3% of the US general population, with high burden for individuals and societies1 (4 to 8-fold increase in standardised mortality rates). Clinically, (cocaine) addiction (or substance use disorder) is defined as the compulsive use of a substance causing clinically and functionally significant impairment (health problems, disability, and failure to meet major responsibilities at work, school, or home). These features constitute the basis of diagnostic criteria. There is no approved medication to treat CocAdd, despite significant advances regarding the mechanisms underpinning the neurobiology of chronic cocaine self-administration in rodents. CocAdd is defined as a maladaptive and compulsive reward-seeking behaviour related to cocaine. The loss-of-control over drug use and associated urges (craving) is such that 75-90% people with CocAdd report that they have relapsed within one year after inpatient detoxification. It is thus crucial to develop innovative and precise biomarkers to predict the liability to relapse if we are to develop efficient treatment strategies against this devastating disorder. Relapse is a key player in the chronicity of addiction in general and, as such, is the core therapeutic target of any therapy against addiction . Attached to an ongoing study of the neuroimaging signature of CocAdd relapse, we implemented an auxiliary study to draw blood samples from patients with CocAdd undergoing hospital detoxification and followed for up to three months after, so as to collect genetic material. The 'OBSCOC' protocol thus provides biological samples at entry and 15, 30 and 90 days after. These samples are aimed for characterising the whole RNome, miRNome and ChipSeq profile of these patients, who all provided written informed consent for the genetic study and for extensive clinical and sociodemographic assessment as well. We hypothesised that specific changes of gene expression between time points could either predict increased risk for/precocity of or announce imminent relapse. Thus they could serve, on the longer-term, as biomarkers and/or therapeutic targets.

Related team publications :
Icick R, Vorspan F, Karsinti E, Ksouda K, Lépine JP, Brousse G, Mouly S, Bellivier F, Bloch V. Gender-specific study of recurrent suicide attempts in outpatients with multiple substance use disorders. J Affect Disord. 2018 Dec 1;241:546-553. doi: 10.1016/j.jad.2018.08.076. Epub 2018 Aug 13. PubMed PMID: 30153638.
Sakae DY, Marti F, Lecca S, Vorspan F, Martín-García E, Morel LJ, et al. The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens. Mol Psychiatry. 2015 Nov;20(11):1448–59
Vorspan F, Bellais L, Romo L, Bloch V, Neira R, Lépine J-P. The Obsessive-Compulsive Cocaine Scale (OCCS): a pilot study of a new questionnaire for assessing cocaine craving. Am J Addict. 2012 Aug;21(4):313–9.
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Project Type : Medium
Status : In Progress

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