Fig. 5.
Low-dose metformin-dependent AMP-activated protein kinase (AMPK) activation does not affect normal expression of serotonin type 2A receptor (5-HT2A)-induced phrenic motor facilitation (pMF). A: representative traces of compressed integrated phrenic burst amplitude throughout the experimental protocol in 2.5 mM Met + artificial cerebrospinal fluid (ACSF, n = 6)- and 2.5 mM Met + 5-HT2A (n = 4)-treated rats. Gray broken line in each trace represents baseline amplitude of phrenic burst activity, and arrows on top indicate time of it 5-HT2A receptor agonist or ACSF injections in rats pretreated with 2.5 mM metformin. Met (2.5 mM) + ACSF group is the same reported in Fig. 2. B: %change in phrenic burst amplitude (vs. baseline) at 30, 60, and 90 min after last it injection. C: delta (vs. baseline) in integrated phrenic burst amplitude at 90 min after last it injection. D: respiratory frequency at baseline and 30, 60, and 90 min after last it injection. E: end-tidal CO2 level at apneic and at recruitment threshold among experimental groups. Data are presented as means ± SD. Mixed 2-way ANOVA or 1-way ANOVA was used for overall group comparison (with Tukey’s adjustment when necessary), and differences were considered significant at P < 0.05. *Met (2.5 mM) + 5-HT2A receptor agonist different from baseline. #Met (2.5 mM) + 5-HT2A different from 2.5 mM Met + ACSF.