Acute effects of D-fenfluramine on simultaneous measures of aggressive escape and impulsive responses of adult males with and without a history of conduct disorder

Rationale: The role of serotonin in human aggression was evaluated by administering D-fenfluramine and comparing the effects on laboratory measures of aggression, escape and impulsivity among subjects with and without a history of conduct disorder. Methods: Ten male subjects with a history of criminal behavior participated in experimental sessions that measured aggressive and impulsive responses. Five subjects had a history of childhood conduct disorder (CD+) and five control subjects did not. Aggression was measured using the Point Subtraction Aggression Paradigm (PSAP), which provides subjects with an aggressive, escape and monetary L reinforced response options. Impulsive responses were measured using a paradigm that gives subjects choices between small rewards after short delays versus larger rewards after long delays. Results: Acute doses (0.1, 0.2 and 0.4 mg/kg) Of D-fenfluramine produced significant decreases in aggressive responses in CD+ subjects and large decreases in escape responses for CD+ subjects and smaller decreases for control subjects. Impulsive responses were decreased slightly and monetary reinforced responses were not changed in either group. Decreases in aggressive responses were not selective, since escape responses were also decreased, but such effects could not be attributed to a non-specific sedative action because monetary reinforced responses were increased and reaction times were decreased, indicative of central nervous system stimulation. Conclusions: Release of serotonin by D-fenfluramine is the possible mechanism for reductions in aggressive responses. These results are consistent with a large body of data linking reduced serotonin function and aggressive behavior.