title: An mTph2 SNP gives rise to alterations in extracellular 5-HT levels, but not in performance on a delayed-reinforcement task.
abstract: 5-Hydroxytryptamine (5-HT) is an important neurotransmitter mediating many aspects of cognition and behaviour. One psychology in which 5-HT plays an important role is impulsive responding. Recently, we have demonstrated that variation in an aspect of impulsive behaviour, namely delayed gratification, has a clear genetic contribution. Here, we examined the neurobiological relevance of a recently discovered single nucleotide polymorphism (SNP) in the murine gene tryptophan hydroxylase (mTph2) by analysing extracellular levels of 5-HT in medial prefrontal cortex (mPFC) and ventral striatum (VS), key brain regions for impulsive behaviours. The allelic variants were associated with systematic effects on baseline 5-HT efflux in the mPFC and VS. We then went on to examine whether the mTph2 allelic variants gave rise to differences in impulsive behaviour. However, the mTph2 genotype, and therefore presumably baseline brain levels of 5-HT, did not predict impulsive choice, as indexed by sensitivity to delayed reinforcement. Consequently, the data do not support a role for the mTph2 C1473G polymorphism on this aspect of impulsive behaviour. Instead, they indicate that perturbations of the 5-HT system via heritable traits may have differential consequences for qualitatively distinct aspects of impulsive behaviour.
authors.affiliation: Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB2 4AT, UK. anthony.isles@bbsrc.ac.uk
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Isles
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Hathway
authors.forename: Trevor
authors.initials: T
authors.lastname: Humby
authors.forename: Carlos
authors.initials: C
authors.lastname: de la Riva
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kendrick
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Wilkinson
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D005838:Genotype; D007175:Impulsive Behavior / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012054:Reinforcement, Psychology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D012701:Serotonin; D014365:Tryptophan Hydroxylase