Lehr Erich
Department of Pulmonary Research, Boehringer Ingelheim Pharma KG, 55216 Ingelheim am Rhein, Germany.
Psychopharmacology (Berl). 2002 Oct;163(3-4):495-500. doi: 10.1007/s00213-002-1199-7. Epub 2002 Aug 29.
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.
The present study was aimed at investigating behavioral effects of pramipexole that may indicate possible antidepressant properties.
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.
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.
Based on other preclinical data and initial clinical results, we speculate that these effects may reflect anti-anhedonic/antidepressive properties of pramipexole.
普拉克索是一种多巴胺激动剂，可选择性地与多巴胺D(3)和D(2)受体结合。有证据表明，除了对帕金森病有有益作用外，该化合物在解决与抑郁症相关的症状方面可能也有价值。
本研究旨在调查普拉克索可能表明具有抗抑郁特性的行为效应。
我们测量了不同剂量的普拉克索对雌性NMRI小鼠在经过2分钟固定间隔（FI2）时间表的长期条件反射后夜间活动和操作性反应的影响。
目前的数据表明，有效剂量的普拉克索在给药后的第一小时会抑制小鼠夜间活动，随后会提高其活动水平。经过长期的FI条件反射后，一些小鼠在强化之前转变为反应降低的模式（“低时间控制”），而另一些小鼠则在强化之前保持典型的高反应增加（“高时间控制”）。此外，低口服剂量的普拉克索会增加“低时间控制”小鼠在强化之前的操作性行为，而“高时间控制”小鼠的操作性反应模式保持不变。
基于其他临床前数据和初步临床结果，我们推测这些效应可能反映了普拉克索的抗快感缺失/抗抑郁特性。
