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. 2009 Oct 21;29(42):13264–13273. doi: 10.1523/JNEUROSCI.1907-09.2009

Figure 3.

Figure 3.

Effect of the PLC inhibitor U73122, the PKA inhibitor H89, the α2AR antagonist idazoxan, and the DOP antagonist naltrindole on the ability of CLON, DELT, and the CLON-DELT combination to inhibit nociceptive thermal responses in the tail flick test. High-efficacy doses of CLON and DELT as well as the low-dose CLON-DELT combination were tested under control conditions (light bars) and in the presence of U73122 (3 nmol i.t., dark bars), H89 (6 nmol i.t., vertical striped bars), idazoxan (10 nmol i.t., downward diagonal stripes), and naltrindole (8.8 nmol i.t., upward diagonal stripes). A, The upstream inhibitor of PLC, U73122, abolished the inhibitory effects of the agonists administered alone (76.0 ± 3.9% vs 4.6 ± 1.6% inhibition for CLON and 78.1 ± 5.7% vs 25.7 ± 3.7% inhibition for DELT in the presence of U73122) as well as the synergistic effect of their low-dose combination (69.6 ± 3.3% vs 17.0 ± 7.1% inhibition in the presence of U73122). B, Pretreatment with the PKA inhibitor, H89, had no effect on either CLON administered alone (74.1 ± 5.1% vs 64.9 ± 3.0% inhibition in the presence of H89) or the low-dose combination (82.5 ± 4.5% vs 72.9 ± 3.8% inhibition for in the presence of H89). Pretreatment with H89 reduced the effect of DELT administered alone (88.4 ± 4.2% vs 40.8 ± 6.2% inhibition for DELT in the presence of H89). C, Pretreatment with the α2AR antagonist, idazoxan, completely reversed the effect of CLON administered alone (75.7 ± 6.3% vs 0.2 ± 1.5% inhibition in the presence of idazoxan), and reduced the effects of both DELT alone (87.9 ± 4.4% vs 37.3 ± 4.5% inhibition in the presence of idazoxan) and the CLON-DELT combination (95.4 ± 2.6% vs 53.0 ± 4.4% inhibition in the presence of idazoxan). D, Pretreatment with the DOP antagonist, naltrindole, had no effect on CLON administered alone (74.2 ± 4.5% vs 64.7 ± 4.4% inhibition in the presence of naltrindole), but reduced the inhibitory effect of DELT administered alone (85.3 ± 5.9% vs 22.1 ± 2.4% inhibition in the presence of naltrindole). Pretreatment with naltrindole also reduced the effect of the CLON-DELT combination (92.3 ± 4.0% vs 44.6 ± 3.7% inhibition in the presence of naltrindole). Error bars represent mean ± SEM (n = 6 animals/dose). *p < 0.05; Student's t test.