Nowak Przemysław, Labus Łukasz, Kostrzewa Richard M, Brus Ryszard
Department of Pharmacology, Medical University of Silesia, H. Jordana 38 St., 41-808 Zabrze, Poland.
Pharmacol Biochem Behav. 2006 May;84(1):3-7. doi: 10.1016/j.pbb.2006.03.024. Epub 2006 May 3.
Repeated treatments of rats with the dopamine (DA) D2 receptor agonist quinpirole, consistently produce long-lived DA D2 receptor supersensitization, by the process that has been termed priming. Rats so-primed in ontogeny behaviorally demonstrate adulthood enhancement of low-dose quinpirole-induced yawning. Because 1) dopaminergic neurons originate in midbrain nuclei (substantia nigra and ventral tegmental area), and 2) noradrenergic neurons originate in pontine (locus coeruleus) and medullary areas, it might be presumed that these two monoaminergic systems are independent, not interdependent. However, in the present study we demonstrate that there was an attenuation of quinpirole-enhanced yawning at 8 weeks in rats that were 1) primed by repeated neonatal quinpirole HCl treatments (50 microg/kg per day SC) during the first ten days of postnatal ontogeny, and 2) lesioned at 3 days after birth with DSP-4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride, 50 mg/kg SC). Dose-effect curves indicated a 23-45% reduction in yawning by DSP-4 treatment of quinpirole-primed rats, acutely treated as adults with quinpirole (25, 50, or 100 microg/kg). Effectiveness of DSP-4 is reflected by the 95% and 99% reductions in norepinephrine contents of frontal cortex and hippocampus, respectively (HPLC/ED method). The findings are supportive of a modulatory role of noradrenergic fibers on dopamine receptor priming (supersensitization) in rat brain.
用多巴胺（DA）D2受体激动剂喹吡罗反复处理大鼠，通过一种被称为启动的过程，持续产生长期的DA D2受体超敏反应。在个体发育过程中经如此启动的大鼠在行为上表现出成年期低剂量喹吡罗诱导的打哈欠增强。因为1）多巴胺能神经元起源于中脑核团（黑质和腹侧被盖区），且2）去甲肾上腺素能神经元起源于脑桥（蓝斑）和延髓区域，所以可能推测这两个单胺能系统是独立的，而非相互依存的。然而，在本研究中我们证明，在出生后个体发育的前十天经反复皮下注射新生大鼠盐酸喹吡罗（50微克/千克/天）启动，且在出生后3天用DSP-4（N-2-氯乙基-N-乙基-2-溴苄胺盐酸盐，50毫克/千克皮下注射）损伤的大鼠，在8周时喹吡罗增强的打哈欠有减弱。剂量效应曲线表明，用DSP-4处理经喹吡罗启动的大鼠（成年后急性给予喹吡罗，剂量为25、50或100微克/千克），打哈欠减少23%-45%。额叶皮质和海马去甲肾上腺素含量分别降低95%和99%（高效液相色谱/电化学检测法），这反映了DSP-4的有效性。这些发现支持去甲肾上腺素能纤维对大鼠脑中多巴胺受体启动（超敏反应）具有调节作用。
