Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice.
BACKGROUND
Pramipexole is a dopamine agonist which binds selectively 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.


OBJECTIVE
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.
Lehr
Erich
E
Department of Pulmonary Research, Boehringer Ingelheim Pharma KG, 55216 Ingelheim am Rhein, Germany. lehr@ing.boehringer-ingelheim.com
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D052160:Benzothiazoles; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D000077487:Pramipexole; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
D000928:Antidepressive Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; D013844:Thiazoles; D000077487:Pramipexole