Effects of bupropion and pramipexole on cell proliferation in the hippocampus of adrenocorticotropic hormone-treated rats.

The dopamine reuptake inhibitor bupropion and dopamine D2/3 receptor agonist pramipexole have been clinically proven to improve both depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of the dopamine nerve system in this effect. Bupropion and pramipexole significantly decreased the duration of immobility in normal and ACTH-treated rats. We previously demonstrated that the chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation and neurogenesis. In this study, we used the mitotic marker 5-bromo-2'-deoxyridine to investigate the effects of bupropion and pramipexole on cell proliferation in the subgranular zone of the hippocampal dentate gyrus following chronic treatment with ACTH. The ACTH treatment for 14 d decreased adult hippocampal cell proliferation. The chronic administration of bupropion for 14 d blocked the loss of cell proliferation resulting from the chronic treatment with ACTH, whereas pramipexole did not. The administration of bupropion may have treatment-resistant antidepressive properties, which may be partly attributed to the normalization of hippocampal cell proliferation.

The mechanisms of electroconvulsive stimuli in BrdU-positive cells of the dentate gyrus in ACTH-treated rats.

In clinical studies, electroconvulsive stimuli have been associated with improvements in both depression and treatment-resistant depression. In a previous study, treatment with adrenocorticotropic hormone (ACTH) for 14 days decreased adult hippocampal cell proliferation. Furthermore, electroconvulsive stimuli significantly decreased the duration of immobility following repeated administration of ACTH for 14 days in rats. The present study was undertaken to further characterize the mechanism of treatmentresistant antidepressant effects of electroconvulsive stimuli by measuring cell proliferation, brain-derived neurotrophic factor (BDNF) levels, and phosphorylated and total cyclic adenosine monophosphate (cAMP) response element-binding protein (pCREB/CREB) levels in the hippocampus of ACTH-treated rats. Electroconvulsive stimuli increased cell proliferation in both saline-treated and ACTH-treated rats. Mature-BDNF protein levels showed a tendency to decrease in ACTH-treated rats. Electroconvulsive stimuli treatment increased mature-BDNF protein levels in the hippocampus of both saline-treated and ACTH-treated rats. Furthermore, electroconvulsive stimuli increased phospho-Ser133-CREB (pCREB) levels and the ratio of pCREB/CREB in both saline-treated and ACTH-treated rats. These findings suggest that the treatment-resistant antidepressant effects of electroconvulsive stimuli may be attributed, at least in part, to an enhancement of hippocampal cell proliferation.

[Investigation on the mechanisms for the suppression of cell proliferation in the dentate gyrus of the hippocampus in ACTH treated rats].

We previously reported that adrenocorticotropic hormone (ACTH)-treated rats serve as a valuable animal model for tricyclic antidepressant-resistant depressive conditions. The present study was undertaken to investigate the changes in neurogenesis in the hippocampus of ACTH-treated rats. Chronic treatment of ACTH decreased the number of bromodeoxyuridine-labeled cells in the dentate gyrus, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. Furthermore, chronic ACTH treatment also decreased the expression of brain-derived neurotrophic factor, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. These results suggest that antidepressant-resistant depression is caused by the suppression of neurogenesis, and the coadministration of imipramine and lithium, and electroconvulsive stimuli exert an antidepressant-like effect by recovering proliferative signals and neurogenesis.

Effect of pharmacist management on serum hemoglobin levels with renal anemia in hemodialysis outpatients.

The initiation of a pharmacist-implemented management program to ensure appropriate use of erythropoietin-stimulating agents at Mizushima Kyodo Hospital is described. In the present study, we examined the influence of having pharmacists actively manage hemoglobin levels on therapeutic outcome in a retrospective study of 84 outpatients receiving hemodialysis. We compiled in-hospital guidelines for the use of erythropoietin and iron for outpatients with renal anemia. Pharmacists made recommendations, particularly about changes in the dose of erythropoietin and administration of iron preparations, to physicians. Clinical test results were monitored for 12 months (between November 2007 and October 2008) with and without the participation of pharmacists (continuous 6 months). The counseling by pharmacists significantly decreased hemoglobin levels in the high group (>12 g/dl) and significantly increased them in low group (<10 g/dl). Furthermore, it increased hemoglobin levels in the optimal group, suggesting the management of our hospital guidelines. On the other hand, low levels of hemoglobin indicated low levels of albumin. It is suggested that no improvement in hemoglobin levels may indicate low levels of albumin. These findings suggest that the active participation of pharmacists in the management of renal anemia in hemodialysis patients had a great therapeutic impact.

Chronic treatment with imipramine and lithium increases cell proliferation in the hippocampus in adrenocorticotropic hormone-treated rats.

Adult hippocampal neurogenesis is reported to change in animal models of depression and antidepressants. We have used the mitotic marker 5-bromo-2'-deoxyyridine to address the effects of imipramine and lithium on cell proliferation and survival following chronic treatment with adrenocorticotropic hormone (ACTH) in the subgranular zone of the hippocampal dentate gyrus. ACTH treatment for 14 d decreased adult hippocampal cell proliferation and survival. Coadministration of imipramine and lithium for 14 d blocked the loss of cell proliferation but not cell survival resulting from the chronic treatment with ACTH. The coadministration of imipramine and lithium may have treatment-resistant antidepressive properties, which may be attributed, in part, to a normalization of hippocampal cell proliferation.