Background: Cocaine and methamphetamine (METH) are two commonly abused drugs that have behavioral-stimulant properties. These stimulant effects are partially mediated by the dopaminergic system. Recent evidence has suggested that the histamine H3 receptor (H3R) may modulate the release of dopamine induced by METH. The aim of the present study was to examine the role of H3R in the behavioral-stimulant effects of cocaine and METH in mice and monkeys. Methods: Nonhabituated, experimentally naïve mice (n = 5-6) were pretreated with the H3R agonist imetit 30 min before METH or cocaine, and activity was measured for 90 min. The behavioral-stimulant effects of METH and cocaine were also studied in squirrel monkeys (n = 3) under a fixed-interval schedule of stimulus termination. Monkeys were pretreated with imetit 30 min before the peak behavioral-stimulant doses of METH or cocaine derived from individual subjects. Results: Pretreatment with imetit did not affect basal activity in mice. Imetit significantly attenuated the behavioral-stimulant effects of METH, but not cocaine. In monkeys, no dose of imetit tested significantly altered the behavioral-stimulant effects of METH or cocaine. Conclusion: These results suggest a role of H3R in the behavioral-stimulant effects of METH, but not cocaine, in mice and no role in monkeys.
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