Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice. Rx drugs

Drugs online research references

Behav Brain Res. 2003 Sep 15;144(1-2):87-93.
Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice.

Rosa AO, Lin J, Calixto JB, Santos AR, Rodrigues AL.

Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario, Trindade, Florianopolis 88040-900, SC, Brazil.

This study investigated the involvement of NMDA receptors and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like effects of zinc in the forced swimming test (FST). The immobility times in the FST and in the tail suspension test (TST) were reduced by zinc chloride (ZnCl(2), 30 and 10-30 mg/kg intraperitoneal (i.p.), respectively). The doses active in the FST and TST reduced locomotor activity in an open-field. The antidepressant-like effect of ZnCl(2) in the FST was prevented by pre-treatment of animals with guanosine 5'-monophosphate (GMP), ascorbic acid, L-arginine, or S-nitroso-N-acetyl-penicillamine (SNAP), but not with D-arginine, administered at doses that per se produced no anti-immobility effect. The immobility time of mice treated with ZnCl(2)+MK-801 was not different from the result obtained with ZnCl(2) or MK-801 alone, but ZnCl(2)+imipramine had a greater effect in the FST than administration of either drug alone. Pre-treatment of animals with a sub-threshold dose of ZnCl(2) prevented the anti-immobility effect of MK-801, ketamine, GMP, L-arginine or N(G)-nitro-L-arginine (L-NNA), but did not alter the effect of imipramine or fluoxetine. Taken together, the results demonstrate that zinc produced an antidepressant-like effect that seems to be mediated through its interaction with NMDA receptors and the L-arginine-NO pathway.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12946598&dopt=Abstract

note: kwd match prozac online literature

nils.go.jp

Age-related changes in the release and uptake activity of presynaptic axon terminals of rat locus coeruleus (LC) noradrenergic neurons were studied in the frontal cortex using an extracellular single unit recording technique in vivo. Clonidine, a selective alpha(2) adrenergic agonist, and nisoxetine, a selective noradrenaline uptake inhibitor, were infused locally into the frontal cortex to examine the effects of these drugs on release and uptake activities of the axon terminals of LC neurons. Although the infusion of clonidine produced a marked suppression of release, the effect did not change with age. Infusion of nisoxetine caused an inhibition of uptake, but the effect was attenuated in aged rats. These results suggest that the release activity mediated by the presynaptic autoreceptor did not change with age, but the uptake activity mediated by the NA transporter declined with age in the axon terminals of LC neurons.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12812843&dopt=Abstract

note: kwd match prozac online literature

ncl.ac.uk

Both glucocorticoids and selective serotonin reuptake inhibitors (SSRIs) alter aspects of 5-HT function including somatodendritic 5-HT1A autoreceptor sensitivity. Many depressed patients prescribed SSRIs have pre-existing flattened diurnal gluococorticoid rhythm. In these patients, interactions between flattened glucocorticoid rhythm and chronic SSRIs, which impact on the SSRI's ability to elevate forebrain 5-HT, may alter clinical efficacy. To address this issue rats underwent implantation of slow-release corticosterone (75 mg pellet s.c.) (to flatten the glucocorticoid rhythm) or sham surgery, and injection of fluoxetine (10 mg/kg/day i.p., 12 days) or vehicle. Using microdialysis in the frontal cortex we found that (21 h after the last injection) extracellular 5-HT was elevated in fluoxetine- or corticosterone-treated animals, but not in those treated with corticosterone plus fluoxetine. In fluoxetine-treated animals, blockade of terminal reuptake by local perfusion of fluoxetine increased 5-HT to the same level as it did in controls, suggesting normal terminal 5-HT release after chronic fluoxetine. However, 5-HT levels following local reuptake blockade in both the corticosterone and corticosterone plus fluoxetine groups were lower than controls, suggesting a corticosterone-induced decrease in terminal release. Finally in fluoxetine, corticosterone, and corticosterone plus fluoxetine groups, there was marked 5-HT1A receptor desensitization, evidenced by attenuation of the decrease in 5-HT release following systemic fluoxetine injection. The data indicate that, despite desensitization of 5-HT1A autoreceptors, concurrent flattened glucocorticoid rhythm compromises the ability of SSRIs to elevate forebrain 5-HT. These findings suggest a potential mechanism for the reduced antidepressant efficacy of SSRIs in those patients with pre-existing glucocorticoid abnormalities.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12784107&dopt=Abstract

note: kwd match prozac online literature

Herbs and Pharmaceuticals Online || Hair Million herbal formula for hair loss and hair growth || Antibiotics and prescription medications online literature ||