The olfactory bulbectomized rodent has long been one of the preferred animal models of depression and certain other neuropsychiatric diseases. In fact, it is considered unparalleled, by some, in the search for antidepressant medication and the literature generated about the model is prodigious. We have revisited the “syndrome” of behavioral sequela following bulbectomy choosing ecologically valid tests likely to be underpinned with evolutionarily preserved neural circuits. Our test battery included measurements of activity, intermale aggression, pleasure seeking, stress/fear and non-spatial memory. The emphasis was on the timetable of syndrome emergence, since this has been understudied and bears on the widely held belief that non-olfactory effects dominate. Our results largely agree with previous reports describing the behavioral syndrome in that we document bulbectomized mice as hyperactive, non-aggressive and fearless. However, we did not find deficits in memory as have frequently been reported in previous studies. Notably, our results revealed that some syndrome behaviors—including the hallmark of hyperactivity—appear immediately or soon after surgery. This rapid appearance casts doubt on the widely held view that compensatory reorganization of limbic and prefrontal cortical areas following bulbectomy underlies the syndrome. Rather, hyperactivity, non-aggressiveness, reduced fear and diminished sucrose preference in the olfactory bulbectomized mouse find ready explanations in the loss of smell that is the immediate and irreversible outcome of bulbectomy. Finally, after a critical consideration of the literature and our results, we conclude that the olfactory bulbectomy model lacks the validity and simplicity previously credited to it. Indeed, we deem this lesion unsuitable as a model of most neuropsychiatric diseases since its effects are at least as complex and misunderstood as the disorders it is purported to model.

嗅球切除的啮齿动物长期以来一直是抑郁症和某些其他神经精神疾病的首选动物模型之一。事实上，在寻找抗抑郁药物方面，一些人认为它是无与伦比的，关于该模型的文献非常多。我们重新审视了球茎切除术后行为后遗症的“综合征”，选择了可能以进化保留的神经回路为基础的生态有效测试。我们的测试电池包括对活动、男性间攻击性、寻求乐趣、压力/恐惧和非空间记忆的测量。重点是综合征出现的时间表，因为这一直没有得到充分研究，并且与非嗅觉效应占主导地位的普遍看法有关。我们的结果在很大程度上与之前描述行为综合征的报告一致，因为我们将切除球茎的小鼠记录为多动、无攻击性和无畏。然而，我们没有发现之前研究中经常报告的记忆缺陷。值得注意的是，我们的结果显示，一些综合征行为——包括多动症的标志——会在手术后立即或不久出现。这种快速的出现使人们对广泛持有的观点提出质疑，即球茎切除术后边缘系统和前额叶皮质区域的代偿性重组是该综合征的基础。相反，嗅球切除小鼠的多动、非攻击性、恐惧减少和蔗糖偏好减少，可以在嗅觉丧失中找到现成的解释，这是球切除术的直接和不可逆转的结果。最后，在对文献和我们的结果进行批判性考虑后，我们得出结论，嗅球切除模型缺乏以前认为的有效性和简单性。事实上，我们认为这种病变不适合作为大多数神经精神疾病的模型，因为它的影响至少与它声称要建模的疾病一样复杂和被误解。