Chronic Fluoxetine Treatment Attenuates Stressor-Induced Changes in Temperature, Heart Rate, and Neuronal Activation in the Olfactory Bulbectomized Rat

Abstract

The olfactory bulbectomized (OB) rat is a well-characterized animal model that exhibits a number of behavioral and neurochemical changes that have relevance to clinical depression. Hyperactivity in the open field is the most widely used parameter assessed in this model and is reversed following chronic, but not acute, antidepressant treatment. This study investigated OB-induced alterations in heart rate, body temperature, and neuronal activation following open-field exposure and the impact of chronic treatment with fluoxetine on these parameters. Upon placement in the open field, OB rats exhibited a characteristic hyperactivity response. Heart rate and body temperature were increased in sham-operated rats following open-field exposure, a predictable response to stress, which was significantly reduced in OB rats. Moreover bulbectomy reduced open field-induced cFOS expression in the basal nucleus of the stria terminalis while concurrently increasing expression in the hippocampus, amygdala, paraventricular nucleus of the thalamus, and dorsal raphe nucleus. Chronic fluoxetine treatment (10 mg/kg subcutaneous once daily for 5 weeks) attenuated all of these OB-associated changes. In conclusion, OB rats exhibit alterations in behavior, body temperature, heart rate, and neuronal activation in response to open-field exposure, which are reversed following chronic fluoxetine administration. These results identify stress-sensitive regions within the brain which are altered following bulbectomy and which may underlie the abnormal behavioral and physiological changes observed in this rodent model of depression.

Effect of newly synthesized 1,2,4-triazino[5,6-b]indole-3-thione derivatives on olfactory bulbectomy induced depression in rats

“…Similar effects were seen in the present study. OBX rats showed reduced BPM indicating loss of vagus control [33] . Imipramine and fluoxetine significantly increased heart rate as reported earlier [33] .…”

Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression

“…injection of this drug on the depression-like symptoms induced by OBX in Wistar rats, to compare the efficacy of these two methods of nicotine administration. We further compared the effect of nicotine to the anti-depressant like effects of TMS, because it is well known that the OBX-rodent model responds well to other anti-depressant therapies [15,21], and we wanted to test the effect of TMS, which has emerged as an alternative to electroconvulsive therapy for the treatment of human depression [13]. Moreover, repetitive TMS reduces immobility time in the FST, which further supports an antidepressant effect for this therapy [22].…”

Minocycline modulates neuropathic pain behaviour and cortical M1–M2 microglial gene expression in a rat model of depression

“…Bilateral olfactory bulbectomy (OB) was performed on rats anaesthetised with isoflurane (Abbot Laboratories, UK [3% induction, 1.5% maintenance in 0.5 l/min O 2 ]) as described previously (Roche et al, 2007, Burke et al, 2010, Burke et al, 2013a. In brief, two burr holes of 2mm diameter were drilled into the skull, 5mm rostral to bregma and 2mm lateral to the midline and the olfactory bulbs removed by gentle aspiration.…”

“…OB-induced hyperactivity in the open field has been shown to be attenuated selectively following chronic but not acute, antidepressant administration (Roche et al, 2007, Song and Leonard, 2005, Kelly et al, 1997. Two weeks following sham/OB surgery, animals were placed singly into a brightly-lit (lux 200) novel open field arena (diameter 75cm) with a white floor (plastic-covered wood flooring) and reflective walls for a 5 minute period.…”

“…Two weeks following sham/OB surgery, animals were placed singly into a brightly-lit (lux 200) novel open field arena (diameter 75cm) with a white floor (plastic-covered wood flooring) and reflective walls for a 5 minute period. Locomotor activity (distance moved, cm) was assessed using a computerised video tracking system (EthoVision®, Version 8 Noldus, Netherlands) as previously described (Burke et al, 2013a, Burke et al, 2010, Roche et al, 2007.…”