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 TT genotype 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.
RCT Entities:
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 TPH1rs1799913, TPH2rs4290270, and SLC6A45-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 TPH1rs1799913 A allele reported greater subjective response to cocaine for 'stimulated' and 'access' relative to the CC genotype group. Those carrying the TPH2rs4290270 A allele reported higher 'good effect' and lower 'depressed' effect relative to the TT genotype group. Those carrying the SLC6A45-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.
Authors: Vadim Yuferov; Orna Levran; Dmitri Proudnikov; David A Nielsen; Mary Jeanne Kreek Journal: Ann N Y Acad Sci Date: 2010-02 Impact factor: 5.691
Authors: Xian-Zhang Hu; Robert H Lipsky; Guanshan Zhu; Longina A Akhtar; Julie Taubman; Benjamin D Greenberg; Ke Xu; Paul D Arnold; Margaret A Richter; James L Kennedy; Dennis L Murphy; David Goldman Journal: Am J Hum Genet Date: 2006-03-28 Impact factor: 11.025
Authors: David A Nielsen; Sandra Barral; Dmitri Proudnikov; Scott Kellogg; Ann Ho; Jurg Ott; Mary Jeanne Kreek Journal: Behav Genet Date: 2008-01-08 Impact factor: 2.805
Authors: Riley B Longtain; David P Graham; Mark J Harding; Richard De La Garza Ii; David A Nielsen Journal: Behav Brain Res Date: 2021-11-16 Impact factor: 3.332
Authors: Vadim Yuferov; Eduardo R Butelman; Matthew Randesi; Wim van den Brink; Peter Blanken; Jan M van Ree; Mary Jeanne Kreek Journal: Neuropsychiatr Dis Treat Date: 2021-02-25 Impact factor: 2.570