Department of Pharmacology, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
Life Sci. 2013 Feb 7;92(2):119-24. doi: 10.1016/j.lfs.2012.11.005. Epub 2012 Nov 15.
Olfactory bulbectomy (OBX) in rodents represents a valuable experimental model of depression. This study was designed to shed further light on the impact of putative serotonergic neuronal degeneration in OBX mice and to assess the effect of a widely used antidepressant on serotonergic related behavioral changes induced by OBX.
Adult male ddY mice were subject to bilateral OBX or sham surgery. The serotonin (5-HT)(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) enhanced a head-twitch response (HTR) in OBX mice. Effects of 5-HT(2A), 5-HT(2C) antagonists and fluvoxamine were observed in OBX mice following DOI administration.
The HTR elicited by the administration of DOI (0.5 mg/kg and 1 mg/kg, i.p.) was increased about twofold in OBX mice when compared with controls on the 14th day after the surgery. The injection of ketanserin (0.025 mg/kg, i.p.), a 5-HT(2A) receptor antagonist, inhibited the enhancement of the DOI-induced HTR after OBX. Likewise, the administration of SB 242084 (1 mg/kg, s.c.), a 5-HT(2C) receptor antagonist, also inhibited the DOI-induced HTR in OBX mice. Chronic but not acute treatment with the antidepressant fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), suppressed the enhancement of DOI-induced HTR after OBX.
These findings indicate that OBX, and the subsequent degeneration of neurons projecting from the olfactory bulb, caused a supersensitivity of 5-HT(2A/2C) receptors which may be involved in symptoms of depression.
嗅球切除术（OBX）在啮齿动物中代表了一种有价值的抑郁实验模型。本研究旨在进一步阐明 OBX 小鼠中假定的 5-羟色胺能神经元变性的影响，并评估一种广泛使用的抗抑郁药对 OBX 诱导的与 5-羟色胺相关的行为变化的影响。
成年雄性 ddY 小鼠接受双侧 OBX 或假手术。5-羟色胺（5-HT）（2A/2C）受体激动剂 2,5-二甲氧基-4-碘苯丙胺（DOI）增强 OBX 小鼠的头部抽搐反应（HTR）。在 DOI 给药后观察 OBX 小鼠中 5-HT（2A）、5-HT（2C）拮抗剂和氟伏沙明的作用。
与手术后第 14 天的对照组相比，DOI（0.5mg/kg 和 1mg/kg，ip）给药后 OBX 小鼠的 HTR 增加了约两倍。5-HT（2A）受体拮抗剂酮色林（0.025mg/kg，ip）的注射抑制了 OBX 后 DOI 诱导的 HTR 增强。同样，5-HT（2C）受体拮抗剂 SB 242084（1mg/kg，sc）的给药也抑制了 OBX 小鼠中 DOI 诱导的 HTR。慢性而非急性给予选择性 5-羟色胺再摄取抑制剂（SSRI）氟伏沙明可抑制 OBX 后 DOI 诱导的 HTR 增强。
这些发现表明，OBX 及其随后的嗅球投射神经元变性导致 5-HT（2A/2C）受体超敏，这可能与抑郁症状有关。
