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Changes to the binding properties of cortical N-methyl-D-aspartic acid (NMDA) and beta-adrenergic receptors have both been reported as potential indicators of antidepressant activity. In the present investigation we examined the effects of the noradrenaline reuptake inhibitor, reboxetine, the serotonin reuptake inhibitor, sertraline, alone and in combination on the binding properties of cortical NMDA receptors and cortical beta1-adrenoceptors following 14 days of treatment in the olfactory bulbectomized rat model of depression. A decrease in the potency of glycine to displace the strychnine insensitive glycine antagonist [3H] 5,7 dichlorokynurenic acid (5,7 DCKA) was observed in cortical homogenates of OB rats when compared to sham-operated controls. Similarly, treatment with the combination of reboxetine and sertraline for 14 days produced a decrease in the potency of glycine when compared to vehicle treated controls. By contrast neither olfactory bulbectomy or drug treatment significantly altered basal or glycine enhanced binding of the non-competitive NMDA antagonist [3H] MK-801 in cortical homogenates. Reboxetine alone, and in combination with sertraline, down-regulated [3H]-CGP 12177 (a selective beta-adrenoceptor antagonist) binding in both OB and sham-operated animals. The lack of a bulbectomy effect in the [3H] CGP-12177 binding assay, and the fact that olfactory bulbectomy and antidepressant treatments produce a similar change to the potency of glycine at the NMDA receptor, suggests that these tests do not provide a neurochemical marker for either the behavioral hyperactivity deficit or antidepressant response in the model.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11129111&dopt=Abstract
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Braz J Med Biol Res. 2001 Jan;34(1):57-64.
Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats.
Gomez R, Huber J, Tombini G, Barros HM.
Divisao de Farmacologia, Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Porto Alegre, RS, Brasil.
Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11151029&dopt=Abstract
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Rev Neurol. 2000 Nov 16-30;31(10):919-22.
[Comparison of the effects of the administration of fluoxetine and sertraline on the immune markers of the mu opioid receptor in the rat brain]
[Article in Spanish]
Acebes I, Echevarria E, Abecia LC, Barbero I, Maza JL, Casis L.
Departamento de Fisiologia, Facultad de Farmacia, Universidad del Pais Vasco, Vitoria-Gasteiz, Alava, Espana.
INTRODUCTION: Chronic fluoxetine or imipramine administration in rats can generate a similar increase in the number of neural cells immunostained for mu opioid receptors in several prosencephalic regions. OBJECTIVE: The aim of the present work was to describe the effects of chronic sertraline administration on mu opioid receptor immunostaining in several rat brain prosencephalic regions, in order to compare with previously described fluoxetine effects. MATERIALS AND METHODS: Experimental animals were chronically administered with sertraline (i.p.). An immunocytochemical method, with the aid of a computerized image analysis system, was used in order to measure the number of neural cells immunostained for mu opioid receptors in several prosencephalic regions. RESULTS: Although chronic sertraline administration in rats generates a significant increase in the number of neural cells immunostained for mu opioid receptors in the caudatus-putamen, dentate gyrus, lateral septum and the frontal, parietal and piriform cortices, slight regional differences, with respect to fluoxetine action, were found. Thus, a more marked action on parietal cortex and lateral septum, and a lesser action on the frontal cortex, were found. CONCLUSION: Regional differences in sertraline effects, with respect to fluoxetine, could be related to a lesser incidence of psychomotor impairment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11244683&dopt=Abstract
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