Evidence for the effect of serotoninergic and dopaminergic gene variants on stress levels in horses participating in dressage and harness racing
S. Negro A D , M. J. Sánchez-Guerrero A , E. Bartolomé A , M. Solé A B , M. D. Gómez A , A. Membrillo C , A. Molina C and M. Valera AA Departamento de Ciencias Agro-Forestales, Universidad de Sevilla, Ctra. Utrera km 1, 41013-Sevilla, España.
B Department of Animal Breeding and Genetics, SLU University, Ulls Väg 26, 750 07-Uppsala, Sweden.
C Departamento de Genética, Universidad de Córdoba, Ctra. Madrid-Cadiz Km.396, 14071-Córdoba, España.
D Corresponding author. Email: snegram@gmail.com
Animal Production Science 59(12) 2206-2211 https://doi.org/10.1071/AN18358
Submitted: 31 May 2018 Accepted: 28 April 2019 Published: 11 October 2019
Abstract
Eye temperature assessed with infrared thermography is an adequate tool for stress level assessment in sport horses’ competitions having a moderate heritability. Serotonin and dopamine signal transduction-linked gene variants have been associated with anxiety-related traits in several species. In this study we examined the association between 10 gene variants in BDNF, COMT, HTR1A, TPH2 and SLC6A4 genes (and the haplotypes at SLC6A4 gene) with stress level (measured with eye temperature and heart rate) in 270 animals, 135 Spanish Trotter Horses (STH) participating in trotting races and 135 ‘Pura Raza Español’ (PRE) horses in dressage. Association analyses were performed using a unified mixed model (counting for population structure and individual relatedness) for the whole population and for each horse breed. The g.43865600G > A intronic gene variant located 11.0 kb downstream from the transcription start site of SLC6A4 gene was associated with an increase in eye temperature before competition with a relative contribution of this gene variant of 38.8% (P = 0.001), 31.8% just after (P = 0.001) and 29.8% 2 h after the competition (P = 0.003). In STH, the g.43865600G > A gene variant showed the same association with eye temperature before (P = 0.001, contribution 27.2%), just after (P = 0.0003, 29.0%) and after the competition (P = 0.002, 17.5%); and the c.*111G > A gene variant located at the 3′UTR region of COMT gene was associated with eye temperature 2 h after the competition (P = 0.001, 22.3%). These results showed that SLC6A4 and COMT gene variants are associated with stress level measured as eye temperature increase during competitions, and may be promising tools for genetic testing against resistance at high stress levels in trotter horses.
Additional keywords: dressage ability, infrared thermography, neurotransmitter, SNP, trotter racing.
References
ANCCE (2012) Specific purebred Spanish horse stud book rules and regulations. BOE no. 127, May 28, 2012.Axelrod J, Reisine TD (1984) Stress hormones – their interaction and regulation. Science 224, 452–459.
| Stress hormones – their interaction and regulation.Crossref | GoogleScholarGoogle Scholar | 6143403PubMed |
Ayala I, Martos NF, Silvan G, Gutierrez-Panizo C, Clavel JG, Illera JC (2012) Cortisol, adrenocorticotropic hormone, serotonin, adrenaline and noradrenaline serum concentrations in relation to disease and stress in the horse. Research in Veterinary Science 93, 103–107.
| Cortisol, adrenocorticotropic hormone, serotonin, adrenaline and noradrenaline serum concentrations in relation to disease and stress in the horse.Crossref | GoogleScholarGoogle Scholar | 21641009PubMed |
Barrey E, Langlois B (2000) How to breed for elite show jumper. In ‘The elite show jumper’. (Ed. A Lindner) pp. 13–23. (Wageningen Academic Publishers: Wageningen, Germany)
Bartolomé E, Cockram MS (2016) Potential effects of stress on the performance of sport horses. Journal of Equine Veterinary Science 40, 84–93.
| Potential effects of stress on the performance of sport horses.Crossref | GoogleScholarGoogle Scholar |
Bartolomé E, Sánchez M, Molina A, Schaefer A, Cervantes I, Valera M (2013) Using eye temperature and heart rate for stress assessment in young horses competing in jumping competitions and its possible influence on sport performance. Animal 7, 2044–2053.
| Using eye temperature and heart rate for stress assessment in young horses competing in jumping competitions and its possible influence on sport performance.Crossref | GoogleScholarGoogle Scholar | 24067493PubMed |
Benjamin J, Liz L, Pattersonz C, Hamer DH (1996) Association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genetics 12, 81–84.
| Association between the D4 dopamine receptor gene and measures of novelty seeking.Crossref | GoogleScholarGoogle Scholar | 8528258PubMed |
Bush V, Middlemiss D, Marsden C, Fone K (2003) Implantation of a slow release corticosterone pellet induces long‐term alterations in serotonergic neurochemistry in the rat brain. Journal of Neuroendocrinology 15, 607–613.
| Implantation of a slow release corticosterone pellet induces long‐term alterations in serotonergic neurochemistry in the rat brain.Crossref | GoogleScholarGoogle Scholar | 12716412PubMed |
Carvajal-Rodriguez A, de Uña-Alvarez J (2011) Assessing significance in high-throughput experiments by sequential goodness of fit and q-value estimation. PLoS One 6, e24700
| Assessing significance in high-throughput experiments by sequential goodness of fit and q-value estimation.Crossref | GoogleScholarGoogle Scholar | 21931819PubMed |
Cook N, Schaefer A, Warren L, Burwash L, Anderson M, Baron V (2001) Adrenocortical and metabolic responses to ACTH injection in horses: an assessment by salivary cortisol and infrared thermography of the eye. Canadian Journal of Animal Science 81, 621 [abstract].
Cooper JJ, Albentosa MJ (2005) Behavioural adaptation in the domestic horse: potential role of apparently abnormal responses including stereotypic behaviour. Livestock Production Science 92, 177–182.
| Behavioural adaptation in the domestic horse: potential role of apparently abnormal responses including stereotypic behaviour.Crossref | GoogleScholarGoogle Scholar |
Dinan TG (1996) Serotonin and the regulation of hypothalamic-pituitary-adrenal axis function. Life Sciences 58, 1683–1694.
| Serotonin and the regulation of hypothalamic-pituitary-adrenal axis function.Crossref | GoogleScholarGoogle Scholar | 8637392PubMed |
Falush D, Stephens M, Pritchard JK (2007) Inference of population structure using multilocus genotype data: dominant markers and null alleles. Molecular Ecology Notes 7, 574–578.
| Inference of population structure using multilocus genotype data: dominant markers and null alleles.Crossref | GoogleScholarGoogle Scholar | 18784791PubMed |
Fernandez SP, Gaspar P (2012) Investigating anxiety and depressive-like phenotypes in genetic mouse models of serotonin depletion. Neuropharmacology 62, 144–154.
| Investigating anxiety and depressive-like phenotypes in genetic mouse models of serotonin depletion.Crossref | GoogleScholarGoogle Scholar | 21945798PubMed |
Gianola D, de los Campos G, Hill WG, Manfredi E, Fernando R (2009) Additive genetic variability and the Bayesian alphabet. Genetics 183, 347–363.
| Additive genetic variability and the Bayesian alphabet.Crossref | GoogleScholarGoogle Scholar | 19620397PubMed |
Gómez M, Valera M, Molina A (2010) Genetic analysis of racing performance of trotter horses in Spain. Livestock Science 127, 197–204.
| Genetic analysis of racing performance of trotter horses in Spain.Crossref | GoogleScholarGoogle Scholar |
Gutiérrez JP, Goyache F (2005) A note on ENDOG: a computer program for analysing pedigree information. Journal of Animal Breeding and Genetics 122, 172–176.
| A note on ENDOG: a computer program for analysing pedigree information.Crossref | GoogleScholarGoogle Scholar | 16130468PubMed |
Hall C, Burton K, Maycock E, Wragg E (2011) A preliminary study into the use of infrared thermography as a means of assessing the horse’s response to different training methods. Journal of Veterinary Behavior: Clinical Applications and Research 6, 291–292.
| A preliminary study into the use of infrared thermography as a means of assessing the horse’s response to different training methods.Crossref | GoogleScholarGoogle Scholar |
Hausberger M, Muller C, Lunel C (2011) Does work affect personality? A study in horses. PLoS One 6, e14659
| Does work affect personality? A study in horses.Crossref | GoogleScholarGoogle Scholar | 21479184PubMed |
Hong K-W, Weiss A, Morimura N, Udono T, Hayasaka I, Humle T, Murayama Y, Ito S, Inoue-Murayama M (2011) Polymorphism of the tryptophan hydroxylase 2 (TPH2) gene is associated with chimpanzee neuroticism. PLoS One 6, e22144
| Polymorphism of the tryptophan hydroxylase 2 (TPH2) gene is associated with chimpanzee neuroticism.Crossref | GoogleScholarGoogle Scholar | 21765945PubMed |
Hori Y, Tozaki T, Nambo Y, Sato F, Ishimaru M, Inoue‐Murayama M, Fujita K (2016) Evidence for the effect of serotonin receptor 1A gene (HTR1A) polymorphism on tractability in thoroughbred horses. Animal Genetics 47, 62–67.
| Evidence for the effect of serotonin receptor 1A gene (HTR1A) polymorphism on tractability in thoroughbred horses.Crossref | GoogleScholarGoogle Scholar | 26763159PubMed |
Kinnunen S, Laukkanen R, Haldi J, Hanninen O, Atalay M (2006) Heart rate variability in trotters during different training periods. Equine Veterinary Journal 38, 214–217.
| Heart rate variability in trotters during different training periods.Crossref | GoogleScholarGoogle Scholar |
Koenen E, Aldridge L, Philipsson J (2004) An overview of breeding objectives for warmblood sport horses. Livestock Production Science 88, 77–84.
| An overview of breeding objectives for warmblood sport horses.Crossref | GoogleScholarGoogle Scholar |
Lesch K-P, Bengel D, Heils A, Sabol SZ (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531.
| Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.Crossref | GoogleScholarGoogle Scholar | 8929413PubMed |
Mandelli L, Serretti A, Marino E, Pirovano A, Calati R, Colombo C (2007) Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders. International Journal of Neuropsychopharmacology 10, 437–447.
| Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders.Crossref | GoogleScholarGoogle Scholar | 16756688PubMed |
Maron E, Lang A, Tasa G, Liivlaid L, Toru I, Must A, Vasar V, Shlik J (2005) Associations between serotonin-related gene polymorphisms and panic disorder. International Journal of Neuropsychopharmacology 8, 261–266.
| Associations between serotonin-related gene polymorphisms and panic disorder.Crossref | GoogleScholarGoogle Scholar | 15670397PubMed |
McBride SD, Mills DS (2012) Psychological factors affecting equine performance. BMC Veterinary Research 8, 180
| Psychological factors affecting equine performance.Crossref | GoogleScholarGoogle Scholar | 23016987PubMed |
Mota M, Oliveira H, Silva R (1998) Genetic and environmental factors that affect the best time of thoroughbred horses in Brazil. Journal of Animal Breeding and Genetics 115, 123–129.
| Genetic and environmental factors that affect the best time of thoroughbred horses in Brazil.Crossref | GoogleScholarGoogle Scholar |
Munsters CC, Visser KE, van den Broek J, van Oldruitenborgh-Oosterbaan MMS (2012) The influence of challenging objects and horse-rider matching on heart rate, heart rate variability and behavioural score in riding horses. Veterinary Journal 192, 75–80.
| The influence of challenging objects and horse-rider matching on heart rate, heart rate variability and behavioural score in riding horses.Crossref | GoogleScholarGoogle Scholar |
Negro S, Bartolomé E, Molina A, Solé M, Gómez MD, Valera M (2018) Stress level effects on sporting performance in Spanish trotter horses. Research in Veterinary Science 118, 86–90.
| Stress level effects on sporting performance in Spanish trotter horses.Crossref | GoogleScholarGoogle Scholar | 29421489PubMed |
Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS (2013) Genome-wide analysis reveals selection for important traits in domestic horse breeds. PLOS Genetics 9, e1003211
| Genome-wide analysis reveals selection for important traits in domestic horse breeds.Crossref | GoogleScholarGoogle Scholar | 23349635PubMed |
Piszczek L, Piszczek A, Kuczmanska J, Audero E, Gross CT (2015) Modulation of anxiety by cortical serotonin 1A receptors. Frontiers in Behavioral Neuroscience 9, 1–10.
| Modulation of anxiety by cortical serotonin 1A receptors.Crossref | GoogleScholarGoogle Scholar |
Reif A, Lesch K-P (2003) Toward a molecular architecture of personality. Behavioural Brain Research 139, 1–20.
| Toward a molecular architecture of personality.Crossref | GoogleScholarGoogle Scholar | 12642172PubMed |
Sánchez MJ, Bartolomé E, Valera M (2016) Genetic study of stress assessed with infrared thermography during dressage competitions in the Pura Raza Español horse. Applied Animal Behaviour Science 174, 58–65.
| Genetic study of stress assessed with infrared thermography during dressage competitions in the Pura Raza Español horse.Crossref | GoogleScholarGoogle Scholar |
Schmidt A, Möstl E, Wehnert C, Aurich J, Müller J, Aurich C (2010) Cortisol release and heart rate variability in horses during road transport. Hormones and Behavior 57, 209–215.
| Cortisol release and heart rate variability in horses during road transport.Crossref | GoogleScholarGoogle Scholar | 19944105PubMed |
Stein MB, Fallin MD, Schork NJ, Gelernter J (2005) COMT polymorphisms and anxiety-related personality traits. Neuropsychopharmacology 30, 2092–2102.
| COMT polymorphisms and anxiety-related personality traits.Crossref | GoogleScholarGoogle Scholar | 15956988PubMed |
Takeuchi Y, Houpt KA (2003) Behavior genetics. Veterinary Clinics of North America. Small Animal Practice 33, 345–363.
| Behavior genetics.Crossref | GoogleScholarGoogle Scholar | 12701516PubMed |
Tunbridge EM, Harrison PJ, Weinberger DR (2006) Catechol-o-methyltransferase, cognition, and psychosis: Val 158 Met and beyond. Biological Psychiatry 60, 141–151.
| Catechol-o-methyltransferase, cognition, and psychosis: Val 158 Met and beyond.Crossref | GoogleScholarGoogle Scholar | 16476412PubMed |
Westergaard GC, Suomi SJ, Chavanne TJ, Houser L, Hurley A, Cleveland A, Snoy PJ, Higley JD (2003) Physiological correlates of aggression and impulsivity in free-ranging female primates. Neuropsychopharmacology 28, 1045–1055.
| Physiological correlates of aggression and impulsivity in free-ranging female primates.Crossref | GoogleScholarGoogle Scholar | 12700686PubMed |
Yu J, Pressoir G, Briggs WH, Bi IV, Yamasaki M, Doebley JF, McMullen MD, Gaut BS, Nielsen DM, Holland JB (2006) A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nature Genetics 38, 203–208.
| A unified mixed-model method for association mapping that accounts for multiple levels of relatedness.Crossref | GoogleScholarGoogle Scholar | 16380716PubMed |
Zierz J, Wintzer H (1996) Acute pain in the horse and one possibility for its objective evaluation. Tierärztliche Praxis 24, 108–112.