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. 2012 Jun;20(3):173-80.
doi: 10.1037/a0026773. Epub 2012 Jan 16.

Behavioral effects of prenatal ketamine exposure in rhesus macaques are dependent on MAOA genotype

John P Capitanio  1 , Laura A Del Rosso, Laura A Calonder, Shelley A Blozis, M Cecilia T Penedo
Affiliations

Behavioral effects of prenatal ketamine exposure in rhesus macaques are dependent on MAOA genotype

John P Capitanio et al. Exp Clin Psychopharmacol. 2012 Jun.

Abstract

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that is used in anesthetic, abuse, and therapeutic contexts. Recent evidence suggests that ketamine may affect not only glutamate systems, but may also act on receptors in the dopamine and serotonin systems. Because monoamine neurotransmitters play important trophic roles in prenatal development, we hypothesized that the behavioral consequences of prenatal exposure to ketamine may be moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. Eighty-two infant rhesus monkeys were identified that had known dates of conception and exposures to ketamine during gestation. Animals were tested at 3-4 months of age on a battery of tests assessing responsiveness to maternal separation, recognition memory, and contact with novel objects. Animals were classified by putative activity levels for the MAOA genotype. The effects of prenatal ketamine exposure were seen only in the context of MAOA genotype. Greater exposure to ketamine resulted in increased activity, less willingness to perform in the memory task, and reduced emotionality and novel-object contact, but only for individuals with the low-activity genotype. Nearly all effects of ketamine were the result of first- and second-trimester exposure. MAOA genotype moderates the role of prenatal ketamine exposure at time points in gestation earlier than have been shown in past research, and is particularly evident for measures of emotionality. These results support the idea that ketamine's use might be best considered in light of individuals' genetic characteristics.

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Conflict of interest statement

All authors indicate that they have no conflicts of interest that impact the research.

Figures

Figure 1
Figure 1
MAOA genotype interacts with number of ketamine exposures in the second trimester for Day 1 Activity.
Figure 2
Figure 2
MAOA genotype interacts with number of ketamine exposures in the first trimester for Day 1 Emotionality.
Figure 3
Figure 3
MAOA genotype interacts with number of ketamine exposures in the first trimester for mean number of 15-second intervals of contact with a novel object per 5-minute block. Data for both sexes are combined for this figure.
Figure 4
Figure 4
MAOA genotype interacts with number of ketamine exposures in the second trimester for the number of balks in the preferential look test.
See this image and copyright information in PMC

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