Fluoxetine reverses depressive-like behaviors and increases hippocampal acetylcholinesterase activity induced by olfactory bulbectomy

Abstract

The olfactory bulbectomy (OB) is an animal model of depression that results in behavioral, neurochemical and neuroendocrinological changes, features comparable to those seen in depressive patients. This study investigated OB-induced alterations in locomotor activity and exploratory behavior in the open-field test, self-care and motivational behavior in the splash test, hyperactivity in the novel object test and novel cage test, and the influence of chronic treatment with fluoxetine (10mg/kg, p.o., once daily for 14days) on these parameters. Fluoxetine reversed OB-induced hyperactivity in the open-field test, locomotor hyperactivity and the increase in exploratory behavior induced by novelty in the novel object and novel cage tests, and the loss of self-care and motivational behavior in the splash test. Moreover, OB decreased the number of grooming and fecal boli in the open-field and novel cage tests, alterations that were not reversed by fluoxetine. OB caused an increase in hippocampal, but not in prefrontal acetylcholinesterase (AChE) activity. Fluoxetine was able to reverse the increase in hippocampal AChE activity induced by OB. Serum corticosterone was increased in SHAM and bulbectomized mice treated with fluoxetine. In conclusion, OB mice exhibited depressive-like behaviors associated with an increase in hippocampal AChE activity, effects that were reversed by chronic treatment with fluoxetine.

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

“…Notably, OBX is known to cause retrograde degeneration of cholinergic neurons in the septum, thereby eliciting anterograde degeneration of cholinergic neurons from the septum to the hippocampus [57]. Numerous studies have reported that OBX induces a reduction in acetylcholinesterase and ChAT levels in the hippocampus in mice [58,59]. In the present study, 2 injections of MMI (75 mg/ kg, i.p.)…”

Fluoxetine: a case history of its discovery and preclinical development

“…OB has been characterised as inducing behavioural and neurochemical changes related to clinical depression, such as motor agitation, cognitive impairment, noradrenergic and serotoninergic dysfunctions [80]. Interestingly, it has been demonstrated that OB-induced depressive behaviour is reversed after chronic fluoxetine administration [81]. Furthermore, it was demonstrated that fluoxetine normalised OB-induced hyperactivity and that it reversed the physiological parameters associated with this model of depression, such as the altered heart rate and body temperature [82].…”

“…After numerous preclinical studies demonstrated the efficacy of fluoxetine as a potent antidepressant [71][72][73][74]79,81], this compound was tested in patients suffering from depression. In one of the first human studies, the clinical efficacy and safety of fluoxetine was compared with imipramine in a double-blind, 5-week, parallel study performed on 40 depressed out-patients.…”

Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways

“…An incision was made in the skin to expose the skull, and holes were drilled in both sides of the midline. The olfactory bulbs were then bilaterally sucked through a hypodermic needle (1.0-1.2 cm long with a rounded tip 0.80 to 1.2 mm in diameter) attached to a syringe (10 mL), with care used to avoid damaging the frontal cortex, as standardized by Machado et al (2012). Any bleeding was ceased and the holes were cleaned with gauze and covered with dental resin.…”