Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity

Noelle Anastasio, S. Liu, L. Maili, Se Swinford, S. D. Lane, R. G. Fox, S. C. Hamon, D. A. Nielsen, Kathryn Cunningham, F. G. Moeller

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cocaine dependence remains a challenging public health problem with relapse cited as a major determinant in its chronicity and severity. Environmental contexts and stimuli become reliably associated with its use leading to durable conditioned responses ('cue reactivity') that can predict relapse as well as treatment success. Individual variation in the magnitude and influence of cue reactivity over behavior in humans and animals suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse. In the present translational study, we investigated the contribution of variation in the serotonin (5-HT) 5-HT2C receptor (5-HT 2CR) system in individual differences in cocaine cue reactivity in humans and rodents. We found that cocainedependent subjects carrying a single nucleotide polymorphism (SNP) in the HTR2C gene that encodes for the conversion of cysteine to serine at codon 23 (Ser23 variant) exhibited significantly higher attentional bias to cocaine cues in the cocaine-word Stroop task than those carrying the Cys23 variant. In a model of individual differences in cocaine cue reactivity in rats, we identified that high cocaine cue reactivity measured as appetitive approach behavior (lever presses reinforced by the discrete cue complex) correlated with lower 5-HT2CR protein expression in the medial prefrontal cortex and blunted sensitivity to the suppressive effects of the selective 5-HT2CR agonist WAY163909. Our translational findings suggest that the functional status of the 5-HT2CR system is a mechanistic factor in the generation of vulnerability to cocaine-associated cues, an observation that opens new avenues for future development of biomarker and therapeutic approaches to suppress relapse in cocaine dependence.

Original languageEnglish
Article numbere369
JournalTranslational Psychiatry
Volume4
DOIs
StatePublished - 2014

Fingerprint

Receptor, Serotonin, 5-HT2C
Cocaine
Cues
Serotonin
Recurrence
Cocaine-Related Disorders
Individuality
Appetitive Behavior
Choice Behavior
Gene Conversion
Prefrontal Cortex
Codon
Serine
Single Nucleotide Polymorphism
Cysteine
Rodentia
Public Health
Biomarkers
Observation

Keywords

  • Attentional bias
  • Cocaine
  • Cue reactivity
  • Prefrontal cortex
  • Serotonin

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience

Cite this

Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity. / Anastasio, Noelle; Liu, S.; Maili, L.; Swinford, Se; Lane, S. D.; Fox, R. G.; Hamon, S. C.; Nielsen, D. A.; Cunningham, Kathryn; Moeller, F. G.

In: Translational Psychiatry, Vol. 4, e369, 2014.

Research output: Contribution to journalArticle

Anastasio, Noelle ; Liu, S. ; Maili, L. ; Swinford, Se ; Lane, S. D. ; Fox, R. G. ; Hamon, S. C. ; Nielsen, D. A. ; Cunningham, Kathryn ; Moeller, F. G. / Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity. In: Translational Psychiatry. 2014 ; Vol. 4.
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