Evidence that conditioned stress enhances outflow of dopamine in rat prefrontal cortex: A search for the influence of diazepam and 5‐HT1A agonists
Evidence that conditioned stress enhances outflow of dopamine in rat prefrontal cortex: A search for the influence of diazepam and 5‐HT1A agonists
复制标题
DOI：
10.1002/(sici)1098-2396(199611)24:3
复制
发表时间：
1996-11
期刊：
影响因子：
2.3
通讯作者：
K. Wȩdzony;M. Maćkowiak;K. Fijał;K. Gołembiowska
中科院分区：
文献类型：
--
作者：
K. Wȩdzony;M. Maćkowiak;K. Fijał;K. Gołembiowska
我们评估了条件应激对大鼠前额叶皮质多巴胺流出的影响。将大鼠暴露于与厌恶性刺激相关的环境-足部电击以与施加足部电击时的条件训练期间观察到的类似方式增强多巴胺的流出。地西泮（2.5和10 mg/kg）剂量依赖性地减少多巴胺流出，并且当以10 mg/kg但非2.5 mg/kg的剂量给药时，减少由条件应激诱发的增强的多巴胺流出。另一方面，ipsapirone（10 mg/kg，但不是2.5 mg/kg）和丁螺环酮（2.5 mg/kg）增加多巴胺的基础流出。当向暴露于条件应激的大鼠给予ipsapirone（10 mg/kg）和丁螺环酮（2.5 mg/kg）时，应激诱发的多巴胺流出升高被消除。2.5 mg/kg剂量的Ipsapirone在测试的应激范例中无效。可以得出结论，条件应激在体内增强大鼠前额叶皮层多巴胺能神经传递，这种作用被地西泮（一种经典的抗焦虑药物）和新型抗焦虑药物伊沙匹隆和丁螺环酮（通过多巴胺能5-HT 1A受体发挥作用）减弱。虽然伊萨匹隆和丁螺环酮阻断了应激诱导的多巴胺流出增强，但这种作用似乎是由于它们对多巴胺基础流出的影响。根据地西泮和5-HT 1A激动剂对各种类型的广泛性焦虑症的可能有效性，讨论了地西泮和5-HT 1A激动剂对基础和应激诱导的多巴胺流出变化的不同影响。© 1996 Wiley利斯公司
We evaluated the impact of conditioned stress on outflow of dopamine in the rat prefrontal cortex. Exposure of rats to an environment associated with aversive stimuli‐foot shock enhanced outflow of dopamine in a similar way as seen during the conditioning session when foot shocks were applied. Diazepam (2.5 and 10 mg/kg) dose‐dependently decreased outflow of dopamine and, when given in a dose of 10 mg/kg, but not 2.5 mg/kg, decreased enhanced dopamine outflow evoked by conditioned stress. On the other hand, ipsapirone (10 mg/kg, but not 2.5 mg/kg) and buspirone (2.5 mg/kg) enhanced basal outflow of dopamine. When ipsapirone (10 mg/kg) and buspirone (2.5 mg/kg) were given to rats exposed to conditioned stress, the stress‐evoked elevation in dopamine outflow was abolished. Ipsapirone in a dose of 2.5 mg/kg was ineffective in the stress paradigm tested. It is concluded that conditioned stress in vivo enhances dopaminergic neurotransmission in the rat prefrontal cortex, this effect being attenuated by diazepam, a classic anxiolytic drug, and by such novel anxiolytics as ipsapirone and buspirone, which operate via serotonergic 5‐HT1A receptors. Although ipsapirone and buspirone blocked stress‐induced enhancement of dopamine outflow, this effect seems to result from their influence on the basal outflow of dopamine. Differential effects of diazepam and 5‐HT1A agonists on basal and stress‐induced alterations in dopamine outflow are discussed in terms of their possible effectiveness in various types of general anxiety disorders. © 1996 Wiley‐Liss, Inc.