Relationships among CSF monoamine metabolite levels, alcohol sensitivity, and alcohol‐related aggression in rhesus macaques

Abstract

AbstractA relationship between alcohol intake and aggressive behavior has been demonstrated in both associational and laboratory studies. Among the factors that contribute to aggression during intoxication are a history of violence and the level of alcohol‐induced stimulation. In humans, excessive alcohol intake and alcoholism are predicted by decreased sensitivity, or a low level of response (LOR), to alcohol. In addition, aggressive behavior, LOR, and alcoholism have been attributed to CNS serotonergic dysfunction. Given that they are both related to diminished CNS serotonin, in this study we wanted to determine whether a low LOR to alcohol would be associated with aggression during intoxication in rhesus macaques. Adolescent rhesus macaques (N=115) received an intravenous dose of ethanol (2.2g/kg) and were scored for their levels of response for 30 minutes. Following provocation by an investigator, animals were then scored for aggressive behaviors (lunges, open‐mouth threats, stares, head‐bobs, and barks) for five minutes. At the approximate age of five years, animals were entered into a free‐access alcohol consumption study, during which they were allowed voluntary access for one hour/day, four days/week to aspartame‐sweetened alcohol or vehicle. Alcohol intake for each subject was determined using a computerized collar, which was detected by a station system that measured individual subject consumption rates. Data were analyzed using regression analyses and t‐tests. Decreased sensitivity to alcohol, alcohol‐induced increases in CSF MHPG, and pre‐alcohol CSF levels of 5–HIAA were associated independently with aggression during intoxication (r= −0.32, P= 0.0006 , r = − 0.29, P=0.01, and r= −0.21, P=0.02, respectively). High rates of alcohol‐related aggression predicted future alcohol consumption (r=0.27, p=0.004), even after controlling for rearing condition and monoamine metabolite concentrations, previously shown in these animals to predict alcohol consumption. By investigating the relationships between LOR, central catecholamine reactivity and function, and alcohol‐induced aggression in alcohol‐naïve nonhuman primates, this report provides evidence that alcohol‐induced stimulation and neurotransmitter‐linked predisposition to impulsive aggression independently contribute to aggression during intoxication. This paper further emphasizes the importance of the nonhuman primate model for studying susceptibility to alcohol‐related aggression and alcoholism, because variables such as prior exposure to alcohol are difficult to control in human subjects. Aggr. Behav. 29:288–301, 2003. © 2003 Wiley‐Liss, Inc.