Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice

Rationale: Pramipexole is a dopamine agonist which binds selectivly to dopamine D-3 and D-2 receptors. There is evidence that, in addition to its beneficial effects in parkinsonism, this compound may also be of value in addressing symptomatology associated with depressive diseases. Objectives: The present study was aimed at investigating behavioral effects of pramipexole that may indicate possible antidepressant properties. Methods: We measured how different doses of pramipexole influence nocturnal locomotion and operant responding after prolonged conditioning of a schedule of FI 2 min (FI2) in female NMRI mice. Results: The present data indicate that active doses of pramipexole inhibit nocturnal locomotion during the first hour after administration and later elevate activity in mice. After prolonged FI conditioning some of the mice changed to a pattern of lowered responding prior to reinforcement ("low temporal control") whereas others maintained the typical high increase of responding prior to reinforcement, ("high temporal control"). Additionally, low oral doses of pramipexole increase operant behavior in "low, temporal control" mice prior to reinforcement leaving the pattern of operant responding of "high temporal control" mice unchanged. Conclusions: Based on other preclinical data and initial clinical results, we speculate that these effects may reflect anti-anhedonic/antidepressive properties of pramipexole.