Calmodulin Dependent Protein Kinase II: An Effector in the Signaling Pathway of Antidepressant-like Behavior Elicited by Ketamine in Combination with Melatonin

• DOI: 10.1124/jpet.122.215840
• Publication Date: 2023-05-18T14:35:08Z
• Authors: Gloria Benítez-King; Armida Miranda-Ri...; Rosa Estrada-Reyes; Citlali Trueta; Jesús Argueta; Julián Oikawa-Sala; Luis Alejandro Co...; Montserrat G. Cercós

<b>Abstract ID 21584</b> <b>Poster Board 473</b> Melatonin (MEL; <i>N</i>-acetyl-5-hydroxytryptamine) and ketamine (KET; 2-(2-chlorophenyl)-2-(methylamino) cyclohexan-1-one) elicit antidepressant-like effects in mice increases neurogenesis the hippocampus (HP) through stimulation of MEL receptors or by blocking NMDA receptors, respectively. Non-effective doses KET administered with non-effective doses, both processes. The alpha isoform Calmodulin-dependent kinase II (CaMKII) is a downstream effector signaling pathways. activates CaMKII stimulates dendrite formation complexity, as well (HP). On other hand, receptor antagonism pospho-CaMKII (p-CaMKII) levels, glutamate (GluR1) expression phosphorylation prefrontal cortex (PC). goal this study was to determine whether combination at that anti-depressant-like behavior GLUR1 pathways HP PC. Male Swiss Webster (25–35 g) were managed under laboratory animal care rules (NIH-85-23, 1985). Vehicle (VEH), either (16 mg/kg), (1.5 mg/kg) alone (1.5/16 mg/kg; KET/MEL) intraperitoneally 10.0 mL/kg body weight, 30 min later submitted forced swimming test (FST). Mice decapitated, PC dissected, homogenized, separated two- one-dimensional electrophoresis, assayed Western blot. We detected αCaMKII, anti-pCaMKII, GluR1 specific primary secondary antibodies coupled FITC RITC. Another group mice, treated described above intracardially perfused 4% paraformaldehyde after FST. sectioned brains cryostat -20°C slices 30-35 μm. Slices stained mentioned nuclei DAPI. Data analyzed Student́s t-test one-way analysis variance (ANOVA). p-values ≤ 0.05 considered significant. identified molecular weights isoelectric point two-dimensional electrophoresis. relative amount increased KET/MEL HP. In PF, protein solely KET/MEL. Also, acidic isoforms significantly showed blot αCaMKII pCaMKII This result confirmed immunostaining No differences observed These results indicate activation selectively caused MEL, an acute administration. we Importantly, dosage tested <i>per se</i> does not produce mice. suggest administration could be mediated increasing GluR1. More experiments are necessary go deeper into mechanism combination. Supported CONACyT Grant 290526 (GBK) 252935 (CT).