PMC

Effect of antidepressants on RTX-induced increases in immobility. Mice were injected with RTX (0.02 mg/kg s.c.) and tested 24 h later in the forced swim test at 41°C. In panel A, in addition to RTX, mice were injected with either saline or amitriptyline (AMI, 10 mg/kg i.p.) 1 h before the RTX and 1 h before the swim. In panel B, mice were injected with saline or ketamine (KET, 50 mg/kg i.p.) 45 min before the RTX and 45 min before the swim. Comparisons between different treatments were performed using one-way ANOVA followed by Tukey’s post-hoc analysis and marked with an asterisk (*) when they differed.

Effect of desensitization of central TRPV1 receptors on forced swims in 26°C and 41°C water. Mice were pretreated i.t. with vehicle or RTX (0.25 µg). The next day, mice were injected with vehicle or a low dose of RTX (0.02 mg/kg s.c.) and tested 24 and 48 h later in a 15-min forced swims in water maintained at either 26°C or 41°C. The time spent immobile during the first 5 min of each swim was measured. Comparisons between different treatments were performed using one-way ANOVA followed by Tukey’s post-hoc analysis and marked with an asterisk (*) when different from each other. Comparisons between same treatments on different days were performed using a paired Students t-test and when significantly different indicated with a pound sign (#) on day 2 (panels B and D).

Effect of resiniferatoxin (RTX) on body temperature. Mice were injected subcutaneously (s.c.) with a single injection of a low dose RTX (0.02 mg/kg), a high dose of RTX (0.1 mg/kg) or an intrathecal (i.t.) injection of RTX (0.25 µ g). In panel A, body temperatures were measured before and 1 h after each injection as well as immediately prior to the forced swim (24 h after the last injection of RTX). In panel B, body temperatures were measured 1 h after receiving each of 5 injections of RTX (0.1 mg/kg s.c.) given at a 3–4 day intervals, to reveal the rate of desensitization to the hypothermic effect of RTX. In panel C, body temperatures were measured 24 h after an i.t. injection of RTX and 1 h after injection of 0.1 mg/kg of RTX s.c. The effect of RTX on body temperature was compared using a one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc analysis, where an asterisk (*) indicates a difference from pre-injection temperatures or from vehicle. Throughout the figures, differences were statistically significant if the probability that it occurred because of chance alone was less than 5% (P<0.05).

Effect of RTX delivered s.c. on immobility in the forced swim test. Mice were injected with vehicle or either a low dose of RTX (0.02 mg/kg) or 3–5 injections of a high dose of RTX (0.1 mg/kg) and then subjected to 2 daily 15-min swims in baths maintained at either 26°C (panels A and B) or 41°C (panels C and D). Immobility in the two vehicle-injected control groups did not differ from each other, so they were pooled. The first forced swim occurred 24 h after the final injection of RTX. Comparisons between the effects of the two doses of RTX and vehicle (on the same day and at the same swim temperature) were performed using one-way ANOVA followed by Tukey’s post-hoc analysis and marked with an asterisk (*) when significant (panels A and C). Comparisons between immobility during swims on day 1 and day 2 (the same treatment and water temperature) were performed using Student’s t-test and marked with a pound sign (#) when significant (panels B and D).