Attention deficit hyperactive disorder (ADHD) is a complex developmental disorder with underlying emotional, attentional and learning disabilities Primary pharmacotherapies for ADHD are central nervous system stimulants, which indirectly enhance monoaminergic (especially dopaminergic) neurotransmission The current therapies provide symptomatic relief, but have restrictive side-effects, including abuse liability Growing anatomical and neurophysiological evidence suggests that histamine H3 receptors may play a modulatory role in monoaminergic transmission and arousal, implying that these receptors could constitute novel targets for the control of ADHD Recent studies suggest that the novel H3 antagonist GT-2331 has beneficial effects in rodent models predictive of anti-ADHD efficacy During the last project period we have evaluated GT-2331 for abuse potential in squirrel monkeys with a history of i v self-administration of cocaine Monkeys initially were tra ined to se lf-administer cocaine (0 1 mg/kg/injection, i v ) on a 30-response fixed-ratio schedule of reinforcement Once robust self-administration of cocaine was maintained consistently from day-to-day, saline was substituted for cocaine until self-administration was no longer maintained Subsequently, self-administration of a 10-fold range of doses of GT 2331 was evaluated Each dose, as well as vehicle, was tested for a minimum of three consecutive sessions and until no consistent trends in response rate were observed from day-to-day Over the range of doses tested, GT-2331 did not maintain self-administration behavior at levels consistently above those maintained by vehicle To the degree that these results can be generalized to people, our findings suggest that the use of GT-2331 for the treatment of ADHD may not be associated with significant abuse liability
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