Inhibition of antidepressant-induced [3H]CDP-diacylglycerol production and phosphoinositide synthesis by neomycin. Slices of rat prefrontal cortex or hippocampus prepared from the same rats were pre-labeled in parallel with [3H]cytidine or [3H]inositol and incubated with indicated concentrations of neomycin, followed by addition of 100 μM fluoxetine (FLU) or 300 μM imipramine (IMI), desipramine (DES), paroxetine (PAR), maprotiline (MAP), or nomifensine (NOM). Accumulated [3H]CDP-diacylglycerol (A) or [3H]phosphoinositides (B) were measured after 90 min. While only the hippocampus data are shown for CDP-diacylglycerol and the cortical data for phosphatidylinositides, each analyte was assessed in each brain region with similar results. Each bar is the mean ± SEM (n = 6). Neomycin significantly and concentration-dependently inhibited drug-induced [3H]CDP-diacylglycerol production and [3H]inositol phospholipid synthesis (ANOVA, p < 0.01 for each drug). The effects of neomycin alone on CDP-diacylglycerol were not significant, whereas it exerted a slight but significant increase at the 0.3 mM concentration (Dunett's, p < 0.01) and decrease at the 3 mM concentration (Dunnett, p < 0.01) in [3H]phosphatidylinositide levels. #p < 0.05; *p < 0.05, compared to respective effects of antidepressant alone by Dunnett test.
Tyeryar et al. BMC Neuroscience 2008 9:12 doi:10.1186/1471-2202-9-12