Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit
Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit
复制标题
DOI：
10.1097/fbp.0b013e32835d5b7a
复制
发表时间：
2013-01-01
影响因子：
1.6
通讯作者：
Szechtman, Henry
中科院分区：
文献类型：
--
作者：
Alkhatib, Ahmad H.;Dvorkin-Gheva, Anna;Szechtman, Henry
本研究探讨了5-羟色胺5-HT 1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）是否可以诱导强迫检查在一个大的开放领域，多巴胺D2/D3受体激动剂喹吡罗。为了诱导强迫性检查，雄性大鼠暴露于8-OH-DPAT（1 mg/kg）、喹吡罗（0.2 mg/kg）或盐水的8次注射。随后，为了评估交叉致敏，大鼠接受8-OH-DPAT或喹吡罗的急性激发。结果表明，8-OH-DPAT治疗诱导强迫检查，并可能有更强的影响，这种行为相比，喹吡罗。然而，8-OH-DPAT和quinpirole之间没有交叉致敏的强制检查和运动的措施。此外，在8-OH-DPAT动物的运动路径的空间分布更局限和不变的quinpirole大鼠;他们的运动敏化率也比quinpirole动物更快。因此，虽然8-OH-DPAT和quinpirole可以诱导强迫检查在一个大的开放领域，结果表明，他们这样做的不同。这表明，8-OH-DPAT和quinpirole可能会产生强迫行为的安全动机电路的不同部分的作用下的强迫症。喹吡罗可能通过直接驱动多巴胺能活动介导检查的动机驱动而诱发强迫性检查行为。相反，8-OH-DPAT可能通过抑制通常使强迫症回路失活的负反馈信号而使激活的动机状态永久化。行为药理学24：65-73（C）2013年威科健康垂直酒吧利平科特威廉姆斯&威尔金斯。
This study investigated whether the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) can induce compulsive checking in a large open field, as does the dopamine D2/D3 receptor agonist quinpirole. To induce compulsive checking, male rats were exposed to eight injections of either 8-OH-DPAT (1 mg/kg), quinpirole (0.2 mg/kg), or saline. Subsequently, to assess cross-sensitization, rats received an acute challenge of 8-OH-DPAT or quinpirole. The results showed that treatment with 8-OH-DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole. However, there was no cross-sensitization between 8-OH-DPAT and quinpirole on measures of compulsive checking and locomotion. Moreover, the spatial distribution of locomotor paths in 8-OH-DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals. Thus, although 8-OH-DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently. It is suggested that 8-OH-DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive-compulsive disorder. Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check. Conversely, 8-OH-DPAT may perpetuate the activated motivational state by inhibiting the serotonergic-negative feedback signals that normally deactivate the obsessive-compulsive disorder circuit. Behavioural Pharmacology 24: 65-73 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.