The Olfactory Bulbectomized Rodent Remains a Valuable Preclinical Model of Depression and Antidepressant Activity

Established over 40 years ago, the olfactory bulbectomized (OB) rodent model has been a widely used and validated preclinical model of depression and antidepressant activity. Due to the anatomical connections of the olfactory bulbs, their removal results in neuronal reorganization in limbic and cortical regions; alterations in neurotransmitter, endocrine, neurotrophin, and neuroimmune systems; and a constellation of behavioral changes, including hyperactivity, anhedonia, and cognitive impairment. Such changes are analogous to those observed in the depressed patients supporting the face validity of this model. Furthermore, similar to the clinical situation, antidepressants reverse neuronal and behavioral changes within in the model following chronic, but not acute, administration, confirming its predictive validity. Recent research has demonstrated that in addition to detecting classical monoaminergic antidepressants, antidepressant-like activity of non-monoaminergic pharmacological agents, such as ketamine, or non-pharmacological interventions, such as exercise and brain stimulation, can be detected in this model. The validity of this model in both mice and rats enables researchers to utilize new and evolving technologies to examine neurobiological underpinnings and treatment responses of relevance to depression using the OB model. This chapter describes in detail the protocol for the establishment of the OB model in rats and mice, examining antidepressant-like activity in the open field test.