Fig. 4.
Effects of naloxone-precipitated withdrawal after 15 days of twice-daily oxycodone (day 16). (A) After 15 days of repeated oxycodone, naloxone (10 mg/kg) attenuated ICSS, and there was an effect of naloxone (F5, 35 = 7.35, P < 0.0001) and an interaction between naloxone time point and frequency (F45, 315 = 1.43, P < 0.05) between 5 and 180 minutes after administration compared with daily baseline responding. Oxycodone (1 mg/kg) was given 2 hours prior to naloxone and is represented by the hashed-line with X symbols (also shown for reference in Fig. 3, A and C) and is not included in statistical analysis. (B) Percent baseline stimulations for the same data set; no stats were conducted on these data because there was no saline control point to use for comparison, but responding is reduced to approximately 50% of daily baseline through 60 minutes after naloxone administration and 75% at 180 minutes, responding returns to baseline at 300 minutes similar to frequency-rate data. Significant differences for frequency-rate curves (A) are denoted by filled symbols (gray: P < 0.05, black: P < 0.01). All values represent means ± S.E.M., and error bars on frequency-rate curves are omitted for clarity (n = 9). oxy, oxycodone.