[Effects of the activation of histamine H3 receptors on the locomotor activity induced by dopaminergic treatment in the reserpine-treated rat model of Parkinson's disease]

ABSTRACT

The present study was designed to investigate the effects of the activation of histamine H3 receptors, by selective agonist, on dopaminergic treatment-induced locomotor behavior in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia. Imetit, histamine H3 receptor agonist reduced the enhanced locomotor activity induced by L-DOPA 100 and 200 mg/kg, in a dose-dependent manner. The number of horizontal counts, following the injection of Imetit 7 mg/kg in combination with L-DOPA 200 mg/kg in reserpinised rats, was 1040 +/- 274 count/2h, which was significantly reduced compared to the horizontal activity following the injection of L-DOPA 200 mg/kg alone in reserpinised rats. The vertical count was significantly reduced by injection of imetit 7 mg/kg in combination with L-DOPA 200 mg/kg [560 +/- 110 count/2h]. The highest dose of Imetit 7 mg/kg that extensively reduced all locomotor parameters tested, did not significantly modify the increase in horizontal or vertical activity produced by quinpirole dopamine D2 agonist. The data suggest that histamine H3 receptor agonists can modulate the behavioural effects of L-DOPA, and may be useful for the treatment of the dyskinesia associated with long-term L-DOPA treatment of Parkinson's disease