Behavioral effects of postnatal ketamine exposure in rhesus macaque infants are dependent on MAOA‐LPR genotype

Abstract

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in pediatric anesthetic and therapeutic practices and veterinary medicine. Previous evidence suggests that exposure to ketamine during sensitive periods of development results in neural apoptosis and atypical behavior. Since monoamine neurotransmitters play important roles in prenatal and early postnatal neural development, and since previous work suggests ketamine can inhibit monoamine transporters, we hypothesized that there would be behavioral consequences of prenatal and early postnatal exposure to ketamine moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. From a large sample of animals (N = 408), we compared groups of rhesus monkeys that had experienced a single exposure to ketamine during prenatal development, an exposure during prenatal development and one postnatal exposure, a postnatal exposure with no prenatal exposure, and no exposures. Animals were classified by putative activity levels for the MAOA genotype and were tested between 3 and 4 months of age on a battery of behavioral tests. Results suggested that animals exposed to ketamine postnatally, at a dose typically used for sedative effects that also had the low-activity variant of MAOA performed poorly on a visual memory test compared to animals with the high-activity variant of the MAOA gene.

Knowledge of Biobehavioral Organization Can Facilitate Better Science: A Review of the BioBehavioral Assessment Program at the California National Primate Research Center

“…We wondered whether lesser exposures might have an impact, and whether rearing in a more naturalistic environment might mitigate some of the adverse effects. Consequently, we examined health records of n = 408 FCR animals and classified them by whether they had one ketamine exposure prenatally and/or one ketamine exposure postnatally (but before we tested the animals in the BBA program, at 3–4 months of age) [ 58 ]. Prenatal exposures were further classified by trimester, based on estimated conception dates (birth date minus 165 days).…”