Effects of d,l-fenfluramine on aggressive and impulsive responding in adult males with a history of conduct disorder

Rationale: The role of serotonin in aggression and impulsivity was examined by administering the serotonin-releasing drug, d,l-fenfluramine and measuring effects on aggressive and impulsive responding under controlled laboratory conditions. Methods: Ten male subjects with a history of conduct disorder and criminal behavior participated in experimental sessions, which measured aggressive and impulsive responses. Aggression was measured using the Point subtraction Aggression paradigm (PSAP), which provides subjects with an aggressive, escape and monetary reinforced response options. Impulsive responses were measured using a paradigm which provided subjects with choices between small rewards after short delays versus larger rewards have long delays. Results: Acute challenge doses (0.2,0.4 and 0.8 mg/kg) of d,l-fenfluramine produced significant dose-dependent decreases in aggressive and impulsive responses. Escape and monetary reinforced responses were not significantly changed. Decreases in aggressive responses were therefore selective, because escape responses were not affected, and could not be attributed to a non-specific sedative action because monetary reinforced responses were slightly increased. Conclusions: Release of serotonin and/or reuptake blockade by d,l-fenfluramine is the possible mechanism for reductions in aggression and impulsivity. These results are consistent with a large body of data linking reduced serotonin function and aggressive behavior and impulsivity.