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Journal Article 2013; 34(8): 773-779 PubMed PMID: 24522018 Citation  Keywords:  Animals, Antidepressive Agents, Second-Generation:pharmacology, Citalopram:pharmacology, Corticotropin-Releasing Hormone:genetics, Cytokines:genetics, Depressive Disorder:drug therapy, Disease Models, Animal, Gene Expression:drug effects, Hypothalamo-Hypo.   

OBJECTIVES: To establish a rat model of post-stroke depression (PSD), and examine expression of genes encoding corticotropin releasing factor (CRF), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in the hypothalamus of PSD rats.

METHODS: Rats were subjected to middle cerebral artery occlusion (MCAO) and chronic mild unpredictable stress (CUMS). Open field test and sucrose preference were used to examine depressive-like behaviors. Observed changes in gene expression levels in the hypothalamus of PSD rats were evaluated.

RESULTS: MCAO with CUMS resulted in reduction of sucrose preference and locomotor activity. Genes encoding TNF-α, IL-1β and CRF were highly expressed in the hypothalamus of rats subjected to MCAO and CUMS. The antidepressant citalopram, a selective serotonin reuptake inhibitor, had inhibitory effects on the expression of the aforementioned genes. We observed a correlation between CRF and IL-1β mRNA levels in the citalopram-treated group of rats.

CONCLUSION: The etiology of PSD is associated with cytokine expression in the hypothalamus and with hypothalamic-pituitary-adrenal axis activity. Citalopram administration inhibited the expression of TNF-α and IL-1β transcripts in the hypothalamus, suggesting that selective serotonin reuptake inhibitors may be appropriate for PSD therapy....

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Controlled Clinical Trial 2007; 28(1): 28-32 PubMed PMID: 17277729 Citation  Keywords:  Adult, Antidepressive Agents, Second-Generation:pharmacology, Circadian Rhythm:drug effects, Depressive Disorder, Major:drug therapy, Female, Fluoxetine:pharmacology, Humans, Male, Melatonin:metabolism, Psychiatric Status Rating Scales, Saliva:metabolism,.   

OBJECTIVES: The purpose of this study is to explore the response of melatonin circadian rhythm to fluoxetine treatment and its relationship with clinical therapeutic effect.

METHODS: This study investigated salivary melatonin in 13 outpatients with major depressive disorder and age- and sex-matched healthy controls. Depressed patients received six weeks fluoxetine (20 mg/day) treatment, and saliva was collected before and four weeks after treatment. In sampling days, a total of 12 time-point salivary melatonin was measured over 24-hours. Multioscillator cosinor model was used to fit the rhythms.

RESULTS: There was no difference of circadian melatonin rhythms in depressed patients, and melatonin was not significantly lower after fluoxetine treatment. To our surprise, the melatonin amplitude (Before minus After) was positively correlated with the improvement in Hamilton Depression Rating Scale (HDRS) scores at day 42 whereas there was no such correlation at day 28.

CONCLUSIONS: Melatonin rhythms were similar between depressed patients and matched healthy controls. The interesting finding that the difference of salivary melatonin amplitude was correlated with the clinical improvement after six weeks fluoxetine treatment deserve further study....

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Journal Article 2006; 27(1-2): 281-287 PubMed PMID: 16648811 Citation  Keywords:  Analgesics, Animals, Antidepressive Agents, Second-Generation:pharmacology, Blood Glucose:metabolism, Diabetes Complications:drug therapy, Diabetes Mellitus, Experimental:blood, Female, Fluoxetine:pharmacology, Hyperalgesia:drug therapy, Male, Mice, Mice,.   

OBJECTIVES: Clinical and experimental trials have demonstrated that some of selective serotonin reuptake inhibitors (SSRIs) have some suspicious effects on blood glucose levels in different directions. Especially fluoxetine and sertraline are studied in this point of view. These drugs are also used in treatment of depression and peripheral neuropathy in diabetic patients. Paroxetine and fluoxetine, members of this drug group, besides having antidepressant effects were shown to have antinociceptive effects in animals and humans. They can be used in the treatment of chronic pain as an adjuvant drug or alone. But less is known about their actions on pain in case of diabetes. The aim of this study is to investigate the antinociceptive effects of fluoxetine and paroxetine in diabetic and non-diabetic mice while monitoring their effects on blood glucose levels.

METHODS: Mice of either sex were randomly used in experiments. The antinociceptive effects of paroxetine and fluoxetine were evaluated using hot plate test both in diabetic and non-diabetic mice. The effects of these drugs on blood glucose levels were also evaluated in another group of mice both in diabetic and non-diabetic mice.

RESULTS: Fluoxetine and paroxetine showed significant antinociceptive effect at all doses and at all times tested in non-diabetic mice, but they could not successfully show this effect in diabetic mice. They also had controversial effects on blood glucose levels.

CONCLUSION: Although they showed increasing or decreasing effects on blood glucose levels in non-diabetic and diabetic mice, they showed antinociception on hot-plate test showing dissociation between blood glucose levels and analgesia....

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