Anxiolytic profile of ropinirole in the rat, mouse and common marmoset

Rationale: Some features of Parkinson's disease are exacerbated by stress a nd anxiety and it is important to understand the effects of dopamine recept or agonists on measures of anxiety. The aim of this study was to assess the effects of the dopamine D-2/D-3 receptor agonist ropinirole in models of a nxiety and depression in the rat, mouse and marmoset. Results: In the rat e levated plus-maze test, ropinirole (0.01-1 mg/kg, i.p.) produced an inverte d-U dose-response curve in the percentage time spent in the open arms. Comp ared with vehicle, ropinirole (0.1 mg/kg) had a significant anxiolytic-like effect, which was similar to that observed with 1.5 mg/kg diazepam. This e ffect was found at doses that did not affect motor behaviour or induce ster eotypy. In the mouse blade and white box test of anxiety, ropinirole (0.1-1 0 mg/kg, i.p.) increased both the rearing time and number of line crosses i n the whits section. This effect reached statistical significance for both measures at a dose of 0.1 mg/kg and suggests an anxiolytic-like action of t he compound. By contrast, the dopamine agonist bromocriptine (0.1-10 mg/kg, i.p.) did not produce significant changes in these behaviours. In the marm oset human threat test, ropinirole (0.01-10 mu g/kg, s.c.) reduced the numb er of postures at all doses tested and this reached statistical significanc e at 10 mu g/kg. Ropinirole did not compromise the effect of amitriptyline in the Porsolt test of depression and in itself produced antidepressant-lik e effects. Conclusions: These data demonstrate that systemic administration of ropinirole produces anxiolytic-like effects ill three separate models i n the mouse, rat and marmoset. This may predict an action of ropinirole in man that would provide a superior profile of action over other presently av ailable anti-parkinsonian agents.