Morelli M., Fenu S., Pinna A., Cozzolino A., Carta A., Di Chiara G.
Department of Toxicology, University of Cagliari, Viale A. Diaz 182, 09100 Cagliari, Italy.
Behav Pharmacol. 1993;4(4):389-397.
In adult rats bearing unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic neurons, a single administration of a dopamine (DA) receptor agonist results in strong sensitization ("priming") of contralateral turning in response to D2 and particularly D1 receptor agonists. In order to investigate the role of distinct environmental cues associated with the effect of the agonist during exposure to the primer, rats bearing 15-day-old unilateral 6-OHDA lesions were primed in their home cage with L-dopa or with saline. L-Dopa but not saline induced medium to low but steady contralateral turning. Three days later, challenge with the D1 agonist SKF 38393 in the home cage also resulted in contralateral turning in the rats previously primed with L-dopa, but not in those primed with saline. In a second experiment rats lesioned with 6-OHDA were primed in two different contexts (hemispheres versus cylinders) with a single administration of the D2/D3 agonist quinpirole (LY 171555: 0.2mg/kg s.c.) or saline. Three days later the rats were placed in hemispheres and tested for contraversive turning in response to saline or to SKF 38393. SKF 38393 elicited high rate contraversive turning independently of the environment where priming with quinpirole took place; on the other hand no conditioned contraversive turning was observed after saline. In a third experiment, the possibility of priming SKF 38393-induced turning by stimulation of nigral or striatal DA receptors was investigated. Rats lesioned unilaterally with 6-OHDA were locally infused on the lesioned side in the substantia nigra with SKF 38393 or in the striatum with quinpirole. Both these treatments elicited contralateral turning, the intranigral injection of SKF 38393 eliciting a stronger and longer lasting contraversive turning than intrastriatal quinpirole. Challenge with SKF 38393 (3mg/kg s.c.) 3 days later induced contralateral turning only in rats previously primed with intrastriatal quinpirole. The results of these studies are consistent with the idea that "priming" is an example of non-associative sensitization induced by stimulation of denervated striatal DA receptors and expressed as an increased efficiency of post-synaptic dopaminergic transduction in the striatum.
在成年大鼠中，其上行多巴胺能神经元存在单侧6-羟基多巴胺（6-OHDA）损伤，单次给予多巴胺（DA）受体激动剂会导致对D2尤其是D1受体激动剂产生的对侧旋转强烈致敏（“启动”）。为了研究在接触启动剂期间与激动剂效应相关的不同环境线索的作用，对有15日龄单侧6-OHDA损伤的大鼠在其饲养笼中用左旋多巴或生理盐水进行启动。左旋多巴而非生理盐水诱导中等至低水平但稳定的对侧旋转。三天后，在饲养笼中用D1激动剂SKF 38393进行激发，也导致先前用左旋多巴启动的大鼠出现对侧旋转，但用生理盐水启动的大鼠则未出现。在第二个实验中，用6-OHDA损伤的大鼠在两种不同环境（半球形与圆柱形）中单次给予D2/D3激动剂喹吡罗（LY 171555：0.2mg/kg皮下注射）或生理盐水进行启动。三天后，将大鼠置于半球形装置中，测试其对生理盐水或SKF 38393的反向旋转反应。SKF 38393引发高频率反向旋转，与用喹吡罗启动时所处的环境无关；另一方面，生理盐水处理后未观察到条件性反向旋转。在第三个实验中，研究了通过刺激黑质或纹状体DA受体启动SKF 38393诱导旋转的可能性。单侧用6-OHDA损伤的大鼠在损伤侧的黑质局部注入SKF 38393或在纹状体中注入喹吡罗。这两种处理均引发对侧旋转，黑质内注射SKF 38393引发的反向旋转比纹状体内注射喹吡罗更强且持续时间更长。三天后用SKF 38393（3mg/kg皮下注射）进行激发，仅在先前用纹状体内喹吡罗启动的大鼠中诱导出对侧旋转。这些研究结果与以下观点一致，即“启动”是由去神经支配的纹状体DA受体刺激诱导的非联合致敏的一个例子，并表现为纹状体中突触后多巴胺能转导效率的提高。
