Pudovkina Olga L, Cremers Thomas I F H, Westerink Ben H C
Department of Biomonitoring and Sensoring, University Center for Pharmacy, 9712 AV Groningen, The Netherlands.
Synapse. 2003 Oct;50(1):77-82. doi: 10.1002/syn.10245.
To investigate the modulation of serotonin release in the dorsal raphe nucleus (DRN) by alpha(1) and alpha(2) adrenoceptors, dual-probe microdialysis was performed in conscious rats. The specific alpha(1) and alpha(2) adrenoceptor agonists and antagonists were locally infused into the DRN via retrograde microdialysis. The release of serotonin was simultaneously sampled from the DRN and prefrontal cortex (PFC). Infusion of the alpha(1) adrenoceptor agonist cirazoline into the DRN (100 microM) produced an increase in the release of serotonin in the DRN to 200% of the basal levels, but no effect was seen in the PFC. After infusion of the alpha(1) adrenoceptor antagonist prazosin into the DRN (100 microM) the release of serotonin decreased in the DRN and PFC to about 40% and 65% of the basal levels, respectively. Infusion of the alpha(2) adrenoceptor agonist clonidine into the DRN (100 microM) slightly but significantly decreased the level of serotonin in the DRN as well as in the PFC to about 70% of the basal levels. Infusion of the alpha(2A) adrenoceptor antagonist BRL 44408 into the DRN (100 microM) caused an increase of serotonin release in the DRN to 270% of the basal levels, but at the same time no changes were seen in the extracellular levels of serotonin in the PFC. The present study demonstrates that alpha(1) as well as alpha(2) adrenoceptors in the DRN modulate the release of serotonin in the DRN, and that alpha(1) adrenoceptors in the DRN are maximally stimulated during resting conditions.
为研究α₁和α₂肾上腺素能受体对中缝背核（DRN）中5-羟色胺释放的调节作用，对清醒大鼠进行了双探针微透析实验。通过逆行微透析将特异性α₁和α₂肾上腺素能受体激动剂和拮抗剂局部注入DRN。同时从DRN和前额叶皮质（PFC）采集5-羟色胺的释放样本。向DRN中注入α₁肾上腺素能受体激动剂可乐唑啉（100微摩尔）可使DRN中5-羟色胺的释放增加至基础水平的200%，但在PFC中未观察到影响。向DRN中注入α₁肾上腺素能受体拮抗剂哌唑嗪（100微摩尔）后，DRN和PFC中5-羟色胺的释放分别降至基础水平的约40%和65%。向DRN中注入α₂肾上腺素能受体激动剂可乐定（100微摩尔）可使DRN和PFC中5-羟色胺水平轻微但显著降低至基础水平的约70%。向DRN中注入α₂A肾上腺素能受体拮抗剂BRL 44408（100微摩尔）可使DRN中5-羟色胺释放增加至基础水平的270%，但同时PFC中5-羟色胺的细胞外水平未见变化。本研究表明，DRN中的α₁以及α₂肾上腺素能受体调节DRN中5-羟色胺的释放，并且DRN中的α₁肾上腺素能受体在静息状态下受到最大程度的刺激。
