Impulsivity, aggression, and neuroendocrine responses to serotonergic stimulation in substance abusers

Alterations in the activity of central serotonergic systems have been implicated in impulsive and aggressive behavior. We examined the neuroendocrine and psychological responses of 24 substance users with differing levels of aggressiveness and impulsivity to the oral administration of an indirect serotonin agonist fenfluramine (60 mg) or placebo given in a double-blind crossover design. All subjects were volunteers on a closed research ward and were abstinent from drugs for a minimum of 5 days. Baseline plasma prolactin (PRL) levels were greater in the groups with higher levels of self-reported aggressiveness and impulsivity. When adjusted for the baseline, PRL and cortisol responses 180 min after fenfluramine administration were significantly elevated in subjects with higher levels of aggressiveness and impulsivity. Peak cortisol levels were correlated with impulsivity. PRL and cortisol responses to fenfluramine were more strongly correlated with impulsivity than aggressiveness. Also, the more impulsive subjects reported a decrease in subjective states of depression, hostility and anxiety after drug treatment. These data further support the hypothesis of altered serotonergic activity in aggressive and impulsive behaviors.