Role of serotonin in the paradoxical calming effect of psychostimulants onhyperactivity

The mechanism by which psychostimulants act as calming agents in humans wit h attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice Lacking the gene encoding the plasma membrane do pamine transporter (DAT) have elevated dopaminergic tone and are hyperactiv e. This activity was exacerbated by exposure to a novel environment. Additi onally, these mice were impaired in spatial cognitive fund:ion, and they sh owed a decrease in locomotion in response to psychostimulants. This paradox ical calming effect of psychostimulants depended on serotonergic neurotrans mission. The parallels between the DAT knockout mice and individuals with A DHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.