ArticleInternational journal of molecular sciences2025
Agmatine Enhances Dorsal Raphe Serotonergic Neuronal Activity via Dual Regulation of 5-HT
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Agmatine is a naturally occurring biogenic amine that acts primarily as an inhibitor of neuronal nitric oxide synthase (nNOS). Previous studies have shown that both acute and chronic agmatine administration induced anxiolytic and antidepressant-like effects in rodents. In the dorsal raphe nucleus (DRN), nitric oxide (NO) donors inhibit serotonergic (5-HT) neuronal activity, with the nNOS-expressing 5-HT neurons showing lower baseline firing rates than the non-nNOS expressing neurons. Our study aimed to test the hypothesis that the psychoactive effects of agmatine are mediated, at least in part, via a mechanism involving the stimulation of the DRN 5-HT neurons, as well as to assess the molecular pathway allowing agmatine to modulate the excitability of 5-HT neurons. Using extracellular in vivo electrophysiology, we demonstrated that both acute (1-3 mg/kg, i.v.) and chronic (40 mg/kg/day, i.p., 14 days) agmatine administration significantly increased the firing rate of DRN 5-HT neurons. Quantitative PCR (qPCR) analysis revealed that chronic agmatine treatment selectively upregulated the expression of serotonin-1B (5-HT
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