Prinssen E P, Koek W, Kleven M S
Centre de Recherche Pierre Fabre, Castres, France.
Eur J Pharmacol. 1998 Aug 14;355(1):19-22. doi: 10.1016/s0014-2999(98)00501-9.
In this study we examined the effects of the preferential dopamine D3 receptor agonist S(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]b enzopyrano-[4,3-b]-1,4-oxazin-9-ol (PD 128,907) on locomotion in mice sensitized to cocaine. In mice repeatedly treated with saline, PD 128,907 induced hypoactivity over a wide dose range (0.01-40 mg/kg); however, after repeated treatment with 40 mg/kg cocaine, higher doses of PD 128,907 (2.5-40 mg/kg) no longer induced hypoactivity whereas the effects of lower doses (0.01-0.16 mg/kg) were not altered. Because lower doses of PD 128,907 are thought to induce hypoactivity via activation of dopamine D3 receptors, the present data suggest that, under conditions where cocaine induces marked sensitization to its locomotor effects, the sensitivity of these receptors is not altered. In contrast, because higher doses of PD 128,907 can activate dopamine D2 receptors, it is conceivable that apparent cross-sensitization to its dopamine D2 receptor agonist properties is responsible for the lack of hypolocomotor effects at high doses. Overall, the results indicate that altered dopamine D3 receptor sensitivity does not play an important role in the expression of cocaine-induced sensitization.
在本研究中，我们检测了选择性多巴胺D3受体激动剂S(+)-(4aR,10bR)-3,4,4a,10b-四氢-4-丙基-2H,5H-[1]苯并吡喃并-[4,3-b]-1,4-恶嗪-9-醇（PD 128,907）对可卡因致敏小鼠运动的影响。在用生理盐水反复处理的小鼠中，PD 128,907在很宽的剂量范围（0.01 - 40 mg/kg）内均可诱导活动减少；然而，在用40 mg/kg可卡因反复处理后，较高剂量的PD 128,907（2.5 - 40 mg/kg）不再诱导活动减少，而较低剂量（0.01 - 0.16 mg/kg）的作用未改变。由于较低剂量的PD 128,907被认为是通过激活多巴胺D3受体来诱导活动减少，目前的数据表明，在可卡因对其运动效应产生明显致敏的情况下，这些受体的敏感性并未改变。相比之下，由于较高剂量的PD 128,907可激活多巴胺D2受体，可以设想，对其多巴胺D2受体激动剂特性的明显交叉致敏是高剂量时缺乏运动减少效应的原因。总体而言，结果表明多巴胺D3受体敏感性的改变在可卡因诱导的致敏表达中并不起重要作用。
