J. D. Higley¹; C. S. Barr¹; S. J. Suomi²
1. Section of Primate Models of Psychopathology, LCTS, NIH, NIAAA Intramural, Poolesville, MD, USA.
2. Laboratory of Comparative Ethology, NICHD, Intramural, Poolesville, MD, USA.

A relationship between alcohol intake and aggressive behavior has been demonstrated in a variety of studies. Primary among the factors that contribute to aggression during intoxication are a previous history of violence and impaired CNS serotonin functioning. In addition, aggressive behavior, a low level of response to alcohol (LOR), and alcoholism have been attributed to impaired CNS serotonergic function.

When adolescent rhesus macaques received an intravenous dose of ethanol (2.2g/kg) and were provoked by an investigator making eye contact, sensitivity to alcohol, alcohol-induced increases in CSF MHPG, and pre-alcohol CSF levels of 5HIAA were associated independently with aggression during intoxication. Studies have also demonstrated gene-environment interactions between 5HTTLPR variation and early environmental deficits on violent behavior. As in humans, there is a serotonin transporter gene promoter biallelic length (short s and long L) polymorphism in rhesus macaques that produces similar decreases in transcriptional efficiency. Macaques with histories of parental deprivation (peer reared PR subjects) have been shown to exhibit impulsive aggression and incompetent social behavior. Not all PR subjects show such deficits. Studies show that subjects with the less efficient 5HTTLPR s allele are particularly sensitive to the effects of parental deprivation, showing high rates of violence as adolescents and adults, whereas the mother reared controls (MR) are undifferentiated by genotype. New studies show that these differences are even more exaggerated when the adolescents are exposed to alcohol, with the PR subjects possessing the s allele showing high rates of aggression. MR subjects were again not differentiated by genotype. More recently we have investigated the developmental history of this phenomenon. Rough and tumble play is widely held to be a socializing influence on aggression in monkeys. We found that play in PR infants with the short allele is infrequent, but in PR subjects with the L allele high rates of play are the norm. As juveniles, low rates of play in the PR subjects and the s allele were predictive of frequent violent behavior. As in the earlier studies, there was gene by environment interaction with the MR subjects not differentiated by genotype in rates of play or violence. Such studies illustrate the emerging evidence that the phenotype is not simply an additive effect of genes and environment, but that genotypic effect on the phenotypic outcome is instead dependent on the environment and that risk for violence and aggression are a complex interplay between impoverished experiences and deleterious genotypes.