[Show abstract][Hide abstract] ABSTRACT: Growing evidence indicates that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of depression. Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis (ALS), directly affects the glutamatergic system. In this study, we investigated the effects of riluzole in olfactory bulbectomy (OBX) rats, an animal model of depression. The olfactory bulbs in rats were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed significant increases in emotionality responses. Single (1st day administration) and subchronic (7th day administration) riluzole treatment (1-10 mg/kg, po) significantly and dose-dependently reduced hyperemotional responses in OBX rats. Both single and subchronic riluzole treatment (10 mg/kg, po) had no significant effects on the emotional responses in sham operated rats. In addition, we demonstrated that single riluzole treatment (10 mg/kg, po) significantly decreased extracellular glutamate levels in medial prefrontal cortex of OBX rats by in vivo microdialysis. We provide the first experimental evidence that riluzole rapidly attenuated hyperemotional responses in OBX rats, an animal model of depression.
No preview · Article · Jan 2011 · Behavioural brain research
[Show abstract][Hide abstract] ABSTRACT: The responses of olfactory bulbectomized (OBX) rats to antidepressant treatment are similar to those of depressed patients since chronic administration of an antidepressant reverses OBX-induced behavioral and physiological changes. Previously, using several animal models, it was demonstrated that single treatment with delta-opioid receptor agonists produced an antidepressant-like effect. This study examined the antidepressant effects resulting from subchronic exposure for 8 days to the delta-opioid receptor agonist SNC80 in an OBX rat model of depression. The olfactory bulbs were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed a significant increase in emotionality score and a decrease in the time spent and entries in the open arm of a plus-maze. In the case of OBX rats, these changes were dose- and time-dependently reversed by chronic SNC80 treatment (1-10 mg/kg, s.c.) for 7 days, as same as desipramine (10 mg/kg, i.p.). Moreover, the concentration of 5-HT and its metabolite 5-HIAA in the frontal cortex, hippocampus, and amygdala were decreased in OBX rats, and these changes were also normalized by SNC80 treatment, rather than desipramine treatment. In addition, SNC80 also significantly reversed the loss of TH-positive cells produced by OBX in the dorsal raphe. In conclusion, we demonstrated that subchronic SNC80 treatment could completely reverse OBX-induced behavioral abnormalities and defects in serotonergic function.
[Show abstract][Hide abstract] ABSTRACT: It has been reported that many of the behavioral and serotonergic neuronal changes observed in olfactory bulbectomy (OBX) were improved by subchronic administration of a variety of antidepressants.
We examined the effects of subchronic treatment with milnacipran, a dual serotonin and noradrenaline reuptake inhibitors (SNRIs) and fluvoxamine, selective serotonin reuptake inhibitors (SSRI) in the OBX-induced hyperemotional behaviors and tryptophan hydroxylase (TPH), rate-limiting enzyme of 5-HT.
The olfactory bulbs were removed by suction. Drugs were administered p.o. once daily for 8 days beginning 14 days post-surgery. The hyperemotionality behaviors of OBX rats were measured by rating scale and in the elevated plus-maze test.
OBX rats, after milnacipran or fluvoxamine treatment, showed significant decrease in the score of hyperemotional responses on 7th day as compared with vehicle-treated OBX rats. In addition, milnacipran and fluvoxamine in OBX rats respectively produced a significant increase in the percentage of time spent in and number of entries into open arms in the elevated plus maze test. Furthermore, when 5-HTnergic neuronal function was examined using antibodies against tryptophan hydroxylase (TPH) following the behavioral tests, fluvoxamine significantly reversed the loss of TPH-positive cells produced by OBX in the dorsal raphe.
We demonstrated that chronic treatment with milnacipran or fluvoxamine was effective to improve both the hyperemotional behavior and the loss of TPH-positive cells seen in OBX rats.
No preview · Article · Jun 2007 · Psychopharmacology