Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: Comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice
Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: Comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice
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DOI：
10.1124/jpet.104.074468
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发表时间：
2005-02-01
影响因子：
3.5
通讯作者：
Caine, SB
中科院分区：
文献类型：
--
作者：
Ralph, RJ;Caine, SB
已经研究了D2受体与多巴胺能药物的治疗用途的关系，精神兴奋作用[表现为惊吓的前脉冲抑制（PPI）降低和运动活动增加]是D2激动剂在大鼠中的标志性行为作用。突变小鼠的遗传学研究可能在这方面的调查是有用的，但是，最近的研究表明，小鼠与大鼠不同的D2激动剂的影响。因此，我们研究了大范围剂量的D2-样激动剂奎诺烷（0.0032 - 5.6 mg/kg）和D1样激动剂R-6-Br-APB [ R（+）-6-溴-7，8-二羟基-3-烯丙基-1-苯基-2，3，4，5-四氢-1H-3-苯并氮杂卓氢溴酸盐]在远交Sprague-Dawley大鼠、远交Swiss-Webster小鼠和近交系129 X1/SvJ、C57 BL/6 J和DBA/2 J小鼠中，而D2激动剂剂量依赖性降低PPI和增加运动的大鼠，这些影响都没有观察到远交或近交系小鼠。相比之下，D1激动剂降低了PPI，增加了Sprague-Dawley大鼠和Swiss-Webster、129 X1/SvJ和C57 BL/6 J小鼠的运动。这两种激动剂都不能降低DBA/2 J小鼠的PPI，尽管D2拮抗剂可增加该品系的PPI。用D2拮抗剂依替氯必利（1 mg/kg）或D1拮抗剂SCH 39166 [（-）反式-6，7，7a，8，9，13 b-六氢-3-氯-2-羟基-N-甲基-5H-苯并[d]萘并-（2，1-B）氮杂卓]（1 mg/kg）预处理可预防大鼠中喹咯烷和小鼠中R-6-Br-AP B的PPI破坏作用，表明两种物种中存在受体相互作用。总之，在远交大鼠中强烈观察到的D2激动剂的精神兴奋作用在几种远交和近交系小鼠中不存在。这些结果可能对研究突变小鼠以研究人类精神功能相关基因具有启示意义。
D2 receptors have been studied in relation to therapeutic uses of dopaminergic drugs, and psychomotor stimulant effects [ as manifested by decreased prepulse inhibition (PPI) of startle and increased locomotor activity] are hallmark behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might be useful in this line of investigation; however, recent studies suggest that mice differ from rats with respect to D2 agonist effects. Accordingly, we studied a wide range of doses of the D2-like agonist quinelorane (0.0032 - 5.6 mg/kg) and the D1-like agonist R-6-Br-APB [ R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl- 2,3,4,5-tetrahydro- 1H-3-benzazepine hydrobromide] (0.032 - 5.6 mg/ kg) in outbred Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J, and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and increased locomotion in rats, neither of these effects was observed in outbred or inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in Sprague-Dawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1 mg/kg) or the D1 antagonist SCH39166 [(-)trans- 6,7,7a, 8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H- benzo[d] naptho-(2,1-b) azepine] (1 mg/kg) prevented the PPI-disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting receptor interactions in both species. In summary, psychomotor stimulant effects of a D2 agonist that were robustly observed in outbred rats were absent in several outbred and inbred strains of mice. These results may have implications for the study of mutant mice to investigate genes involved in psychomotor function in humans.