Genetic moderation of cocaine subjective effects by variation in the TPH1, TPH2, and SLC6A4 serotonin genes

Michelle A. Patriquin, Sara C. Hamon, Mark J. Harding, Ellen M. Nielsen, Thomas F. Newton, Richard De La Garza, David A. Nielsen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Objective This study investigated variants of tryptophan hydroxylase (TPH)1, TPH2, and SLC6A4 in the moderation of the subjective effects of cocaine. Methods Non-treatment-seeking cocaine-dependent individuals (N=66) were intravenously administered saline and cocaine (40 mg) in a randomized order. Participants self-reported subjective effects of cocaine using a visual analog scale starting before administration of saline or cocaine (-15 min) to up to 20 min after infusion. Self-report ratings on the visual analog scale ranged from 0 (no effect) to 100 (greatest effect). Participants were genotyped for the TPH1 rs1799913, TPH2 rs4290270, and SLC6A4 5-HTTLPR variants. Repeated-measures analysis of covariance was used to examine changes in subjective effect scores over time while controlling for population structure. Results Participants carrying the TPH1 rs1799913 A allele reported greater subjective response to cocaine for 'stimulated' and 'access' relative to the CC genotype group. Those carrying the TPH2 rs4290270 A allele reported higher 'good effect' and lower 'depressed' effect relative to the TTgenotype group. Those carrying the SLC6A4 5-HTTLPR S' allele reported greater 'desire' and 'access' compared with the L'L' genotype group. Conclusion These findings indicate that TPH1, TPH2, and SLC6A4 variants moderate the subjective effects of cocaine in non-treatment-seeking cocaine-dependent participants.

Original languageEnglish (US)
Pages (from-to)178-186
Number of pages9
JournalPsychiatric Genetics
Volume27
Issue number5
DOIs
StatePublished - Jun 6 2017

Keywords

  • Cocaine
  • Genetics
  • Polymorphism
  • Serotonin
  • Subjective
  • Substance use
  • Transporter
  • Tryptophan hydroxylase
  • Variant

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Psychiatry and Mental health
  • Biological Psychiatry

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