Fig. 4.
The selective P2rx7 antagonist Brilliant Blue G (BBG) exhibits antidepressant-like activity in the tail suspension test (TST), decreases amphetamine-induced hyperactivity and elevates norepinephrine (NE) level in the amygdala in P2rx7+/+, but not P2rx7−/− mice. (a) The effect of acute BBG treatment on basal immobility in P2rx7+/+ mice (n = 13–15). (b) Effect of sub-acute, 1-wk treatment with BBG on basal immobility in P2rx7+/+ mice. Mice were treated with BBG for 7 d with the daily doses indicated on the abscissa or with saline (Sal) and then submitted to the TST (n = 13–15, * p < 0.05 vs. SAL, one-way analysis of variance (ANOVA), followed by Dunnett's test). (c) Citalopram (Cit; 15 mg/kg), the potent selective serotonin reuptake inhibitor antidepressant, decreased basal immobility in the TST in P2rx7+/+mice (n = 11/group, * p < 0.05 vs. Sal, Student's t test). (d) Effect of 1-wk daily treatment with BBG (25–50 mg/kg i.p.) or Sal on amphetamine induced hyperactivity in P2rx7+/+mice. (n = 10–12/group, ** p < 0.001 vs. Sal, one-way ANOVA followed by Dunnett's test). Citalopram and BBG were administered i.p. 30 min before testing at the doses (mg/kg) indicated on the abscissa. Sal-treated mice were injected with an equal volume of Sal. (e) Effect of sub-acute, 1-wk treatment with BBG (50 mg/kg i.p.) on basal immobility in P2rx7−/− mice. Mice were treated with BBG for 7 d or with Sal and then submitted to the TST (n = 8–10/group). (f) Effect of 1-wk daily treatment with BBG (50 mg/kg i.p.) or Sal on amphetamine-induced hyperactivity in P2rx7−/− mice (n = 10/group). Note that the basal immobility (e) and amphetamine-induced hyperactivity (f) is lower in Sal-treated P2rx7−/− mice than in Sal-treated P2rx7+/+ mice. (g) Sub-acute, 1-wk treatment with BBG (50 mg/kg i.p.) elevates NE, but not 5-HT levels in the amygdala in P2rx7+/+ mice, when compared to Sal-treated mice. Tissue content of NE and 5-HT were analysed by high performance liquid chromatography and are expressed in pmol/mg protein, n = 11–12, ** p < 0.01, Student's t test.
