Depoortere R, Perrault G, Sanger D J
Synthélabo Recherche, Bagneux, France.
Psychopharmacology (Berl). 1996 Apr;124(3):231-40. doi: 10.1007/BF02246662.
This study assessed the effects of IP injections of (+/-) 7-hydroxy-2(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D3 sub-type of receptor, on four behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self-stimulation of the ventral tegmental area (VTA), using the curve-shift procedure 3) operant responding for food under a progressive-ratio (PR) schedule and 4) induction of stereotypies. The effects of (+/-) 7-OH-DPAT were compared to the effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low doses (0.01-0.3 mg/kg), and only apomorphine had clear locomotor stimulant effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently depressed VTA self-stimulation in a similar way, with low doses inducing a fairly parallel rightward shift of the frequency/rate curves and higher doses flattening the curves. In contrast, responding for food under the PR schedule appeared to be differentially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a return to baseline levels with increasing doses (0.3-3 mg/kg); quinpirole showed a tendency to decrease responding over the whole dose-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists induced stereotypies, but there was a difference in the maximal stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower maximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies. Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at low doses, has depressant effects similar to those induced by low doses of the other two DA agonists. Differences in the behavioural effects of higher doses were, however, mostly observed in two procedures, PR responding and induction of stereotypies.
本研究评估了腹腔注射（±）7-羟基-2（N，N-二正丙基氨基）四氢萘（7-OH-DPAT）对大鼠四种行为程序的影响。7-OH-DPAT是一种多巴胺激动剂，据报道它对多巴胺D3亚型受体具有优先亲和力。这四种行为程序分别为：1）自发运动；2）使用曲线位移程序对腹侧被盖区（VTA）进行电刺激自我强化；3）在累进比率（PR）时间表下对食物进行操作性反应；4）刻板行为的诱导。将（±）7-OH-DPAT的作用与非特异性DA激动剂阿扑吗啡以及选择性D2/D3激动剂喹吡罗的作用进行了比较。所有三种多巴胺激动剂在低剂量（0.01 - 0.3 mg/kg）时均降低运动活性，且仅阿扑吗啡在最高测试剂量（3 mg/kg）时有明显的运动兴奋作用。这三种药物以相似的方式剂量依赖性地抑制VTA自我强化，低剂量时诱导频率/速率曲线相当平行地向右移动，高剂量时使曲线变平。相比之下，在PR时间表下对食物的反应似乎受到这三种激动剂的不同影响：7-OH-DPAT产生双相效应，在0.1 mg/kg时杠杆按压最大减少，随后随着剂量增加（0.3 - 3 mg/kg）恢复到基线水平；喹吡罗在整个测试剂量范围内有减少反应的趋势，在0.25至1 mg/kg之间最大效应约为基线的50%，而阿扑吗啡剂量依赖性地减少反应，大鼠在0.3 mg/kg时停止反应。所有三种DA激动剂均诱导刻板行为，但每种配体诱导的最大刻板行为评分存在差异：7-OH-DPAT产生的最大效应低于喹吡罗或阿扑吗啡。这表明这三种多巴胺激动剂各自优先诱导不同类型的刻板行为。总之，这些数据表明，假定的多巴胺D3激动剂7-OH-DPAT在低剂量时具有与低剂量的其他两种DA激动剂相似的抑制作用。然而，高剂量时行为效应的差异主要在两种程序中观察到，即PR反应和刻板行为的诱导。
