| Abstract: | Rationale Recent studies have reported antidepressant-like activities of the dopamine D2/D3agonist pramipexole in the chronic mild stress model and in the forced swim test, suggesting that D3 receptor agonists may represent a new class of antidepressant drugs. However, the relative contribution of D2 or D3 receptors to the activity of pramipexole in these models is unclear.Objectives The aim of the current studies was to explore the role of dopamine D2 and D3 receptors in the activity of pramipexole in the mouse forced swim test.Methods The effect of pramipexole (0.1–3.2 mg/kg) in the mouse forced swim test was examined both in conjunction with D2 and D3 receptor antagonists (haloperidol (0.1–1 mg/kg) and LU-201640 (A-437203, 5.6–17.8 mg/kg), as well as in D3 receptor knockout mice obtained on two different background strains (C57BL/6J and B6129SF2/J). Locomotor activity was also assessed following pramipexole administration.Results Pramipexole produced dose-dependent reductions in immobility in the forced swim test at doses that did not produce generalized increases in locomotor activity. LU-201640, the D3 selective antagonist, failed to block the antidepressant-like effects of pramipexole. In contrast, the efficacy of pramipexole in the forced swim test was completely blocked by the D2 antagonist, haloperidol. No baseline differences were observed between knockout and wild-type mice from either background strain in locomotor activity or in the forced swim test. Furthermore, in both background strains, pramipexole showed similar efficacy in the forced swim test for both wild-type and knockout mice.Conclusions Taken together, these studies suggest that the D2receptor rather than the D3 receptor is important for the antidepressant-like activity observed for pramipexole in the mouse forced swim test.Portions of this work were presented at the 36th Winter Conference on Brain Research, Snowbird, UT, January 26–31, 2003. |
