Hjorth S, Bengtsson H J, Milano S, Lundberg J F, Sharp T
Department of Pharmacology, University of Göteborg, Sweden.
Neuropharmacology. 1995 Jun;34(6):615-20. doi: 10.1016/0028-3908(95)00038-8.
The present study utilized in vivo microdialysis to investigate the importance of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the decreased 5-HT release obtained following administration of the mixed 5-HT1A autoreceptor partial agonist/alpha 1-adrenoceptor antagonist BMY7378, the selective 5-HT1A receptor agonist 8-OH-DPAT and the alpha 1-adrenoceptor antagonist prazosin. BMY7378 (0.25 mg/kg, s.c.), 8-OH-DPAT (0.025 mg/kg, s.c.) and prazosin (0.1-1.0 mg/kg, s.c.) all suppressed ventral hippocampal 5-HT efflux. The BMY7378- and 8-OH-DPAT-induced inhibition of 5-HT release were reversed by a 40 min pre-treatment with either (+/-)pindolol (8 mg/kg, s.c.) or WAY-100635 (0.3 mg/kg, s.c.), to block 5-HT1A autoreceptors. Neitehr of these antagonists altered the prazosin-induced (0.3 mg/kg, s.c.) 5-HT disease.
(i) confirm that both an alpha 1-adrenoceptor antagonist (prazosin) and 5-HT1A autoreceptor stimulants (BMY7378 and 8-OH-DPAT) may reduce cerebral 5-HT release; (ii) support that the BMY7378-induced decrease in 5-HT release results from 5-HT1A autoreceptor agonism, rather than alpha 1-adrenoceptor blockade; and (iii) argue against "physiological" antagonism (i.e. via blockade of beta-adrenoceptors, 5-HT1B receptors or some other mechanism) as an explanation for the reversal by pindolol of 5-HT1A autoreceptor agonist-induced suppression of 5-HT release. These data support the usefulness of pindolol, as well as the more specific compound WAY-100635, to block 5-HT1A autoreceptors.
本研究利用体内微透析技术，来探究5-羟色胺1A自身受体和α1-肾上腺素能受体在混合使用5-羟色胺1A自身受体部分激动剂/α1-肾上腺素能受体拮抗剂BMY7378、选择性5-羟色胺1A受体激动剂8-羟基二丙胺基四氢萘（8-OH-DPAT）和α1-肾上腺素能受体拮抗剂哌唑嗪后5-羟色胺释放减少过程中的重要性。BMY7378（0.25毫克/千克，皮下注射）、8-OH-DPAT（0.025毫克/千克，皮下注射）和哌唑嗪（0.1 - 1.0毫克/千克，皮下注射）均抑制腹侧海马体5-羟色胺流出。BMY7378和8-OH-DPAT诱导的5-羟色胺释放抑制，可通过提前40分钟用（±）吲哚洛尔（8毫克/千克，皮下注射）或WAY-100635（0.3毫克/千克，皮下注射）预处理来阻断5-羟色胺1A自身受体而逆转。这些拮抗剂均未改变哌唑嗪（0.3毫克/千克，皮下注射）诱导的5-羟色胺释放减少。
（i）证实α1-肾上腺素能受体拮抗剂（哌唑嗪）和5-羟色胺1A自身受体兴奋剂（BMY7378和8-OH-DPAT）均可降低大脑5-羟色胺释放；（ii）支持BMY7378诱导的5-羟色胺释放减少是由5-羟色胺1A自身受体激动作用引起，而非α1-肾上腺素能受体阻断作用；（iii）反对将“生理性”拮抗作用（即通过阻断β-肾上腺素能受体、5-羟色胺1B受体或其他某种机制）作为吲哚洛尔逆转5-羟色胺1A自身受体激动剂诱导的5-羟色胺释放抑制作用的解释。这些数据支持吲哚洛尔以及更具特异性的化合物WAY-100635在阻断5-羟色胺1A自身受体方面的有效性。
