Zinc-induced adaptive changes in NMDA/glutamatergic and serotonergic receptors.
Preclinical data indicate the involvement of glutamatergic and serotonergic pathways in the antidepressant activity of zinc. The present study investigated alterations in N-methyl-D-aspartate (NMDA)/glutamatergic and serotonergic receptors (using radioligand binding) induced by chronic treatment (14-day) with zinc hydroaspartate (65 mg/kg). Moreover, the mRNA and protein levels of brain-derived neurotrophic factor (BDNF) were also assessed. Chronic zinc administration reduced the affinity of glycine to glycine/NMDA receptors in the rat frontal cortex and increased the density of 5-HT(1A) and 5-HT(2A) serotonin receptors in the hippocampus and frontal cortex, respectively. These receptor alterations may be in part due to increased BDNF mRNA and protein levels in the rat frontal cortex. These results indicate that chronic zinc treatment alters glutamatergic and serotonergic systems, which is a hallmark of clinically effective antidepressants.
Cichy
Agnieszka
A
Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688 Kraków, Poland.
Sowa-Kućma
Magdalena
M
Legutko
Beata
B
Pomierny-Chamioło
Lucyna
L
Siwek
Agata
A
Piotrowska
Anna
A
Szewczyk
Bernadeta
B
Poleszak
Ewa
E
Pilc
Andrzej
A
Nowak
Gabriel
G
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; D044282:Receptor, Serotonin, 5-HT1A; D001224:Aspartic Acid; D015032:Zinc; D005998:Glycine