CSF 5-HIAA concentrations and social behavior as correlates of alcohol consumption: In a study performed this year, social behavior was studied both prior to and following alcohol consumption to see if alcohol affected social behavior within a social group. The resulting data showed no change in the social dominance hierarchy following alcohol consumption. This, however, may be because the more socially competent, high ranking animals were less likely to consume alcohol to excess, and the low ranking monkeys, who consumed more alcohol, lost no status as a result of their consumption patterns. Mother-reared subjects were more dominant and drank less alcohol than peer-reared subjects. Both baseline 5-HIAA and social dominance rank were negatively correlated with alcohol consumption. Long-term, chronic consumption patterns in socially living macaques: In what is to our knowledge the first study investigating individual differences in long-term, chronic access to alcohol in socially housed nonhuman primates, a number of new findings emerged. While interindividual differences were stable over time, day-to-day variability in rates of alcohol consumption were considerable. Even in subjects which drink alcohol at high rates, there were days when alcohol consumption did not occur at all. Attenuation of Alcohol Consumption Using other Reinforcers: Recent evidence from rodent and human studies suggest that consumption of carbohydrates and sweet substances, including those using artificial sweeteners, may mitigate excessive alcohol consumption. The first phase provided subjects with access to an aspartame-sweetened water solution only; the second allowed subjects to drink alcohol only; and the third gave subjects access to alcohol and aspartame-sweetened water solution simultaneously. Whereas consumption of the sweetened solution remained stable across all conditions, alcohol consumption decreased when subjects had simultaneous access to the sweetened solution and alcohol, indicating that simultaneous availability of a sweetened solution when drinking alcohol may reduce alcohol intake. Cognitive and Temperamental Correlates of Potential Alcohol Preferences: Dr. Allyson Bennett used an automated, computerized joystick video system to measure macaque learning and cognitive abilities. Current work addresses the basis for a deficit found in parentally deprived monkeys by exploring affective components of behaviors that may underlie rearing group differences. Recent data comparing patterns of acquisition of an automated, joystick-video task to performance on a manually-solved puzzle-maze task showed that speed of learning the joystick-video task was not predictive of ability to solve the puzzle-maze. A positive correlation in the amount of effort expended on the two tasks, however, suggested that an underlying dimension of temperament, persistence, was consistently exhibited across tasks. Recently, Dr. Bennett explored the relationship between objective measures of personality and sociality and measures obtained using surveys similar to those in human psychiatric research. Findings from this work showed that peer-reared monkeys were less confident than their mother-reared counterparts. Other assessments showed that the peer-reared male monkeys were the most impulsive when approaching novel, and potentially dangerous objects. Data investigating different methods of measuring social dominance, indicated that subjective ratings provide the same social dominance ranking as objective measures recorded during food competition. Taken together, these results are promising for their potential applications in large-scale screening required for comparative behavioral genetics research. MAO as a Marker for Excessive Alcohol Intake and Type 2 Alcoholism: In a collaboration with Drs. Lars Oreland and Claudia Faulke in Sweden, we investigated the relationship between platelet monoamine oxidase (MAO) activity and excessive alcohol consumption in nonhuman primates. We found that as in humans, nonhuman primates with low platelet MAO consume alcohol to excess, have low CSF 5-HIAA concentrations, and are less competent socially, as measured by low social dominance rank. These findings lend further support to the appropriateness of the nonhuman primate to model biochemical and behavioral features of Type 2 alcoholism, and show that the relationship between low MAO activity and alcoholism is not simply an artifact of smoking. Psychopharmacology Studies: Dr. Bennett collaborated with Dr. Paolo DePetrillo to measure both acute and long-term autonomic changes in response to alcohol and to test the contribution of specific neurochemical systems to individual differences in cardiac signal dynamics. In these studies they found that heart rate variability increases in response to ketamine. This effect is likely due to the NMDA antagonist properties of ketamine, because it is not attenuated by a 5HT3 antagonist, ondansetron, and is nearly identical to the effect of a relatively specific NMDA antagonist, MK801. By contrast, studies showed that alcohol significantly and dramatically decreased heart rate variability. Effects of Essential Fatty Diet on Alcohol Consumption: Our collaboration with Drs. Salem and Hibbeln in the LMBB to investigate the role of essential fatty acids in CNS serotonin functioning continued. Subjects that were fed a diet high in essential fatty acids as infants were shown as adolescents to be less likely to consume alcohol, suggesting long-lasting effects of diets rich in essential fatty acids. These results are preliminary, on a small number of subjects, and will be followed up with investigations of a second cohort this year. Neuroimaging: In an ongoing collaboration with Dr. Dan Hommer, we continued MRI studies of rhesus infants to examine the effect of rearing condition on brain volume. As a follow-up of the MRI brain volume rearing differences, we examined individual differences in brain volumes and correlated that with the plasma cortisol levels previously obtained during a social separation stressor. Consistent with other findings showing the importance of maternal care on the CNS, we found that monkeys that exhibited high levels of cortisol during the social separation stressor possessed smaller brain volumes than monkeys which showed a minimal cortisol response to the separation stress. Neuroanatomy: Drs. Stanley Watson and Juan Lopez at the University of Michigan used classic neuroanatomical techniques to assess neuroanatomical correlates of our subjects with low CSF 5-HIAA concentrations. They quantified glucocorticoid (Gcc), and mineralocorticoid (Mcc) receptors, as well as 5HT transporter (5-HTT), 5-HT1a and 5-HT2a receptors in the hippocampus and prefrontal cortex using in situ hybridization. Our results showed that: 1) In the hippocampus of the PR but not the MR monkeys, the Mcc receptors were downregulated. Similarly, in the prefrontal cortex of the PR but not the MR monkeys, the Gcc receptors were also upregulated. 2) There was an inverse correlation between Gcc receptors in prefrontal cortex and CSF catecholamine metabolites. 3) 5-HTT binding was lower in PR and 5-HT1a receptor mRNA was higher in the prefrontal cortex of the PR subjects when compared to the MR controls. 4) Consistent with our previous PET study showing higher metabolic activity in the frontal cortex of monkeys with low CSF 5-HIAA concentrations, prefrontal cortex 5-HT1a receptor binding was higher in monkeys with low than high CSF 5-HIAA concentrations.
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