Hjorth S
Department of Pharmacology, University of Göteborg, Sweden.
Eur J Pharmacol. 1991 Jun 25;199(2):237-42. doi: 10.1016/0014-2999(91)90463-z.
It has recently been suggested that central 5-HT1A autoreceptors are already desensitised after single-dose 5-HT1A agonist treatment. In turn, this would lead to an attenuated feedback suppression of transmitter release from 5-HT neurones, and thus to enhanced 5-HT synaptic transmission. In the present study in vivo brain microdialysis techniques were used in an attempt to test this hypothesis. The results show that single-dose pretreatment with the reference 5-HT1A receptor agonist 8-hydroxy-2-(din-propylamino)tetralin, 8-OH-DPAT, (i) did not significantly alter the baseline output of 5-HT in the rat ventral hippocampus 24 h later, and (ii) did not alter the release-reducing response to 5-HT1A agonist (8-OH-DPAT, ipsapirone or BMY 7378) challenge under the same conditions. These observations indicate that the functional responsiveness of the 5-HT release-controlling 5-HT1A autoreceptors is maintained after bolus 8-OH-DPAT pretreatment. When related to the acute 8-OH-DPAT-induced reduction in raphe 5-HT1A radioligand binding density recently reported by others, the present results are consistent with a large functional overcapacity of this 5-HT1A receptor population. The mechanism by which 5-HT1A receptor-mediated hypothermia and hyperphagia are rapidly attenuated by a previous large single dose of a 5-HT1A receptor agonist remains to be explained.
最近有人提出，单次给予5-HT1A激动剂治疗后，中枢5-HT1A自身受体已经脱敏。相应地，这将导致5-HT神经元递质释放的反馈抑制减弱，从而增强5-HT突触传递。在本项体内脑微透析技术研究中，试图对这一假说进行验证。结果显示，用5-HT1A受体激动剂参比物8-羟基-2-（二丙基氨基）四氢萘（8-OH-DPAT）进行单次预处理后，（i）24小时后大鼠腹侧海马中5-HT的基线输出未发生显著改变，且（ii）在相同条件下，对5-HT1A激动剂（8-OH-DPAT、ipsapirone或BMY 7378）激发的释放减少反应未发生改变。这些观察结果表明，单次给予8-OH-DPAT预处理后，控制5-HT释放的5-HT1A自身受体的功能反应性得以维持。与其他人最近报道的急性8-OH-DPAT诱导的中缝5-HT1A放射性配体结合密度降低相关，目前的结果与这一5-HT1A受体群体的大量功能过剩相一致。5-HT1A受体介导的体温过低和摄食过多被先前大剂量单次给予5-HT1A受体激动剂迅速减弱的机制仍有待解释。
