In vivo association
between alcohol intoxication, aggression,
and serotonin
transporter availability
in nonhuman primates.
OBJECTIVE: Studies on brain serotonin metabolism in human and
nonhuman primates have indicated that dysfunction of serotonin
transmission may play a role in the biological vulnerability to
dependence on alcohol. Among young men, low sensitivity to alcohol
intoxication predicts subsequent alcohol abuse and dependence.
METHOD: The authors used single photon emission computed tomography
and the radioligand [(I)123]beta-CIT ([(I)123]methyl
3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the
availability of serotonin transporters in 11 male rhesus monkeys,
and the monkeys were genotyped for a functional polymorphism of the
serotonin transporter gene. The 11 monkeys had experienced parental
separation after birth; their behavior and 5-hydroxyindoleacetic
acid (5-HIAA) concentrations in CSF had been assessed regularly.
RESULTS: In the 5-year-old monkeys, there was a significant negative
correlation between beta-CIT binding to serotonin transporters in
the brainstem and 5-HIAA concentrations in CSF. Animals with greater
beta-CIT binding and low CSF 5-HIAA concentrations displayed greater
aggressiveness and were less sensitive to alcohol-induced
intoxication. The genetic constitution of the serotonin transporter
promoter gene did not significantly contribute to the availability
of brainstem serotonin transporters as measured by beta-CIT binding.
CONCLUSIONS: In adult nonhuman primates who underwent early
developmental stress, variables indicating a low serotonin turnover
rate were associated with behavior patterns similar to those
predisposing to early-onset alcoholism among humans.
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