Supplementary Figure 3: Effects of V1a and/or V1b receptor antagonists on tail-flick responses.
(A) The selective V1a antagonist, d(CH2)5Tyr(Me)AVP (4.34 pmol), or saline was injected into the lateral ventricle (i.c.v.) 10 min before daily morphine administration (10 mg/kg/day, s.c.). The development of tolerance was not changed by the V1a antagonist. Tail flick tests were repeated before and 10, 30, 60, and 120 min after morphine administration. The time course of percent maximal possible effect (%MPE) was plotted after morphine injection and area under the curve was calculated. Two-way ANOVA analysis showed no effect of drug, F1,15 = 1.93, P = 0.185; significant effect of time, F2,30 = 70.11, P < 0.0001; no interaction between drug and time, F2,30 = 0.287, P = 0.756. Post hoc analysis by Tukey’s method detected significant decrease, #P < 0.0001 vs. day 1 saline and *P < 0.0001 vs. day 1 d(CH2)5Tyr(Me)AVP. (B) Daily i.c.v. administration of antagonists (dPenTyr(Me)AVP (V1a/Vb antagonist, 4.5 pmol), PhAcALVP (V1aR antagonist, 8.07 pmol) or d(CH2)5Tyr(Me)AVP (V1aR antagonist, 8.68 pmol or saline did not change morphine (10 mg/kg, s.c.) analgesia as assessed by the tail flick test. Two-way ANOVA found no effect of drugs (F3,32 = 0.6351, P = 0.5979). (C) A single administration of saline, vehicle, dPenTyr(Me)AVP (4.5 pmol), or V1b antagonist SSR149415 (10 pmol) into the lateral ventricle did not change morphine dose-response curves in the tail flick test. One-way ANOVA found no effect of antagonist treatment, when responses were compared at each morphine dose separately (F3, 23 = 0.992, P = 0.4139, F3, 23 = 0.068, P = 0.9762, and F3, 23 = 1.081, P = 0.3769 for 2.5, 5 and 10 mg/kg morphine, respectively). Graphs represent the mean ± S.E.M.
