The effect of genotype on attention bias in rhesus macaques, Macaca mulatta, as a welfare indicator.

Abstract

Rhesus macaques, Macaca mulatta, are one of the most commonly used non-human primates in biomedical research in the UK. Their welfare is of great concern for both ethical and quality-of-science reasons. Attention bias (AB), a measure of cognitive bias, assesses whether an individual is stressed, predicts vulnerability to stress, and identifies the effectiveness of interventions to improve well-being. In both humans and macaques, genetic factors can result in variation of behavioural traits, attentional processes and susceptibility to stress-related neuropsychiatric disorders.Here, sixty-five female macaques were genotyped for known variants in the following genes: serotonin transporter (5-HTTLPR; short and long allele), tryptophan hydroxylase 2 (TPH2; short and long allele), monoamine oxidase A (MAOA; 5-, 6- and 7-repeat allele) and mu-opioid receptor (OPRM1; C and G allele). Additionally, sequencing was utilised to identify novel SNPs in the dopamine receptor D4 (DRD4). The 5-HTTLPR short-, TPH2 long-, MAOA 7-repeat and OPRM1 G-allele are low-expressing alleles leading to lower levels of circulating neurotransmitters in the brain, and have been shown to be linked to anxiety, coping mechanisms and vulnerability to stress in macaques. Twenty-nine of the genotyped macaques underwent AB testing with conspecific stimuli (aggressive vs. neutral facial expression, Experiment 1) and stimuli of the facilitie’s veterinarian (photograph vs. pixelated photograph, Experiment 2). Additionally, to assess the effectiveness of habituation to change cognitive responses and improve well-being, females underwent different amounts of habituation to the veterinarian. Video footage was blind-coded for gaze towards stimuli and female’s behaviour following AB tests was recorded. Associations between AB scores, other behavioural measures, and these genetic polymorphisms were investigated in the R package and in SPSS.In Experiment 1, females were more avoidant of aggressive conspecific stimuli when they carried the HTTLPR short- or MAOA 5- and 6-repeat allele and in Experiment 2 females were more avoidant of vet photographs when they carried HTTLPR long- plus TPH2 short alleles only. DRD4 T-allele carriers showed increased amounts of aggressive behaviours and MAOA 7- repeat allele carriers showed increased amounts of affiliative and reduced amounts of maintenance behaviours. Genotype did not have an effect on habituation in Experiment 2, but the more habituation females received the less vigilant they became for the vet photograph.This was the first study showing that genotype impacts on AB in macaques. Advice on further development of methods and future studies is given.