Thomas D N, Nutt D, Holman R B
Reckitt and Colman Psychopharmacology Unit, Medical School, University Walk, Bristol, UK.
Eur J Pharmacol. 1994 Aug 11;261(1-2):53-7. doi: 10.1016/0014-2999(94)90299-2.
The selective alpha 2-adrenoceptor antagonist idazoxan was administered chronically (0.8 mg/kg per h) to rats for a period of 10 days via osmotic minipumps. On day 11, 24 h after removal of the pumps, the rats were anaesthetised and microdialysis probes were implanted into either the frontal cortex or hippocampus. Basal noradrenaline release in the frontal cortex was significantly elevated compared with the saline control group. Each animal was then challenged with idazoxan (10 mg/kg s.c.). Inhibition of presynaptic alpha 2-adrenoceptors resulted in a significant increase in noradrenaline release in the saline control group. However, animals treated chronically with idazoxan, showed a markedly attenuated response to the single dose idazoxan challenge in the frontal cortex. No significant change in either basal release or in response to idazoxan challenge was observed in the hippocampus in the chronic idazoxan-treated animals as compared with the chronic saline control group. Chronic idazoxan administration results in selective enhancement of noradrenaline release in the frontal cortex but not in the hippocampus. This would be consistent with a down-regulation of presynaptic alpha 2-adrenoceptors with the subsequent loss of presynaptic noradrenergic negative feedback inhibition.
通过渗透微型泵对大鼠进行为期10天的选择性α2 -肾上腺素能受体拮抗剂咪唑克生慢性给药（每小时0.8毫克/千克）。在第11天，即移除泵24小时后，将大鼠麻醉并将微透析探针植入额叶皮质或海马体。与生理盐水对照组相比，额叶皮质中的基础去甲肾上腺素释放显著升高。然后给每只动物注射咪唑克生（10毫克/千克，皮下注射）。抑制突触前α2 -肾上腺素能受体会导致生理盐水对照组中的去甲肾上腺素释放显著增加。然而，长期用咪唑克生治疗的动物对额叶皮质中单次剂量咪唑克生激发的反应明显减弱。与慢性生理盐水对照组相比，在慢性咪唑克生治疗的动物中，海马体的基础释放或对咪唑克生激发的反应均未观察到显著变化。长期给予咪唑克生会导致额叶皮质中去甲肾上腺素释放选择性增强，但海马体中不会。这与突触前α2 -肾上腺素能受体下调以及随后突触前去甲肾上腺素能负反馈抑制丧失是一致的。
