Géranton Sandrine M, Heal David J, Stanford S Clare
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Neuropharmacology. 2004 Mar;46(4):511-8. doi: 10.1016/j.neuropharm.2003.10.012.
There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.
有大量证据表明中枢去甲肾上腺素能神经元和5-羟色胺能神经元之间存在功能相互作用。在此，我们使用双探针微透析技术，对自由活动的大鼠进行研究，以比较5-羟色胺对大鼠额叶皮质和下丘脑去甲肾上腺素能传递的影响。我们研究了5-羟色胺合成抑制剂对氯苯丙氨酸（pCPA；它使额叶皮质和下丘脑的5-羟色胺储备均减少）对去甲肾上腺素自发流出以及对d-苯丙胺的去甲肾上腺素能反应的影响，还研究了单胺再摄取抑制剂BTS 54 354的影响。单独使用pCPA预处理，无论是否通过腹腔注射α2拮抗剂阿替美唑（1mg/kg）使α2自身受体失活，均不会影响两个脑区中去甲肾上腺素的自发流出。然而，在额叶皮质中，pCPA预处理增强了对局部注入d-苯丙胺（10μM）的去甲肾上腺素能反应的幅度并延长了其反应时间。相反，pCPA消除了局部注入BTS 54 354（50μM）所诱导的皮质去甲肾上腺素流出增加。在丘脑中，pCPA不影响对这两种药物中任何一种的反应幅度，但确实延长了d-苯丙胺对去甲肾上腺素流出的影响。这些发现表明，5-羟色胺能传递对增加额叶皮质去甲肾上腺素能传递的药物的去甲肾上腺素能反应具有复杂影响，但对下丘脑的影响较小。
