Figure 2
Sertraline, paroxetine and chlorpromazine inhibit pharyngeal pumping in C. elegans. Pumping in day 1 adults was monitored by EPG recordings obtained in a microfluidic chip, in M9 buffer containing 10 mM 5HT (M9-5HT). After 30 min perfusion with M9-5HT the perfusate was switched (grey bars) to M9-5HT containing drug or solvent. Only a portion of the baseline recording period is shown. (A) Excerpts of representative EPG recordings from 4 individual worms switched to (top to bottom): 200 µM sertraline (SRT); 500 µM paroxetine (PXT); 1000 µM chlorpromazine (CPZ); and 0.5% DMSO (CON). In these time-compressed recordings, individual pumps are not visible and pumping appears as a thick, dark line. Insets at an expanded time base (top) show the characteristic decrease in pump frequency and EPG amplitude caused by all 3 drugs. (B,C,D) Concentration- and time-dependence of pump inhibition by SRT, PXT and CPZ, compared to controls. Pump frequency was normalized to the frequency prior to switching perfusate and displayed as mean (line) ± S.E.M. (shading). (E,F,G) Pump frequency from (B,C,D) was plotted against drug concentration at t = 55–60 min (mean ± S.E.M.) and fit using the Hill equation. Number of worms per point (N) shown in parentheses. In every case, there was a significant effect of the drug on pump frequency (p < 10−10; Likelihood Ratio test). (H) Superimposition of the curves in (E,F,G) for comparison. Calculated IC50 values (the drug concentration at which pump frequency was reduced by 50%) are shown. The IC50 value for sertraline differed significantly from the values for paroxetine (p < 10−7) and chlorpromazine (p < 10−4) whereas chlorpromazine and paroxetine IC50s did not differ significantly (p > 0.2; Likelihood Ratio test).
