IN-VIVO ASSOCIATION BETWEEN ALCOHOL-INTOXICATION, AGGRESSION, AND SEROTONIN TRANSPORTER AVAILABILITY IN NONHUMAN-PRIMATES

Studies on brain serotonin metabolism in human and nonhuman primates h ave indicated that dysfunction of serotonin transmission may play a ro le in the biological vulnerability to dependence on alcohol. Among you ng men, low sensitivity to alcohol intoxication predicts subsequent al cohol abuse and dependence. Method: The authors used single photon emi ssion computed tomography and the radioligand [(I)123] beta-CIT ([(I)1 23]methyI 3 beta-(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 seroto nin transporter gene. The 11 monkeys had experienced parental separati on 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-GIT binding to serotonin transporters in the brainstem and 5-HIA A concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were l ess sensitive to alcohol-induced intoxication. The genetic constitutio n of the serotonin transporter promoter gene did not significantly con tribute to the availability of brainstem serotonin transporters as mea sured by beta-CIT binding. Conclusions: In adult nonhuman primates who underwent early developmental stress, variables indicating a low sero tonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans.