Results: 5

1.
Fig. 3.

Fig. 3. From: Extracellular Signal-Regulated Kinase 1/2 Activation Counteracts Morphine Tolerance in the Periaqueductal Gray of the Rat.

ERK1/2 inhibition enhances morphine tolerance. Third-log cumulative microinjections of morphine into the vlPAG on day 3 produced dose-dependent increase in antinociception. This tolerance to the antinociceptive effect of morphine was enhanced by coadministration of morphine and U0126 (D50 = 9.4 μg; n = 14; U0126/Morphine) during the development of tolerance. Nociception was assessed using the hot-plate test, and data were converted to %MPE. Each point on the graph represents the mean hot plate latency score ± S.E.M. for every dose of morphine.

Tara A. Macey, et al. J Pharmacol Exp Ther. 2009 November;331(2):412-418.
2.
Fig. 1.

Fig. 1. From: Extracellular Signal-Regulated Kinase 1/2 Activation Counteracts Morphine Tolerance in the Periaqueductal Gray of the Rat.

Region of the vlPAG where microinjections were administered and ERK1/2 phosphorylation was assessed. Rectangles depict the region of the PAG where ERK1/2 activation was assessed using confocal microscopy [Reproduced with permission from Paxinos G and Watson SJ (2005) The Rat Brain in Stereotaxic Coordinates. Academic Press, New York. Copyright © Elsevier, 2005]. Slices imaged were 50 μm away adjacent to the site of injection. Morphine microinjections were in or immediately adjacent to this rectangle.

Tara A. Macey, et al. J Pharmacol Exp Ther. 2009 November;331(2):412-418.
3.
Fig. 2.

Fig. 2. From: Extracellular Signal-Regulated Kinase 1/2 Activation Counteracts Morphine Tolerance in the Periaqueductal Gray of the Rat.

Increase in hot-plate latency after acute microinjection of morphine into the vlPAG. There was no significant difference in hot-plate latency following saline treatment between U0126 (U/S; n = 10) and saline-pretreated (S/S; n = 9) animals. Acute microinjection of morphine (5 μg/0.4 μl) into the vlPAG caused a significant increase in hot-plate latencies for rats pretreated with saline (S/M; n = 10) or the MEK inhibitor U0126 (U/M; n = 14) [F(3,39) = 22.82; * p < 0.05]. These data indicate that U0126 has no effect on the acute antinociceptive effects of morphine.

Tara A. Macey, et al. J Pharmacol Exp Ther. 2009 November;331(2):412-418.
4.
Fig. 5.

Fig. 5. From: Extracellular Signal-Regulated Kinase 1/2 Activation Counteracts Morphine Tolerance in the Periaqueductal Gray of the Rat.

Inhibition of ERK1/2 phosphorylation enhanced the expression of morphine tolerance. Cumulative dose microinjections of morphine into the vPAG produced a dose-dependent increase in antinociception in morphine-tolerant rats (D50 = 6.0 μg; n = 8; Saline). Pretreatment with U0126 on Trial 5 before assessment of tolerance to morphine caused a rightward shift in the dose-response curve (D50 = 10.8 μg; n = 8; U0126) compared with rats given saline before morphine (* p < 0.05). A within-subjects design was used with saline, and U0126 was administered in a counterbalanced manner on test days (test days were days 3 and 4). Nociception was assessed using the hot-plate test, and data were converted to %MPE. Each point on the graph represents the mean hot-plate latency score ± S.E.M. for every dose of morphine.

Tara A. Macey, et al. J Pharmacol Exp Ther. 2009 November;331(2):412-418.
5.
Fig. 4.

Fig. 4. From: Extracellular Signal-Regulated Kinase 1/2 Activation Counteracts Morphine Tolerance in the Periaqueductal Gray of the Rat.

ERK1/2 activation following repeated morphine microinjections into the vlPAG. Graph, rats were given two pretreatment microinjections on days 1 and 2 of saline (S) or U0126 (U) and saline (S) or morphine (M). Phospho-ERK1/2 fluorescence intensity levels were significantly increased in morphine-pretreated rats (S/M; n = 26 neurons from three animals) compared with saline-pretreated rats (S/S; n = 20 neurons from three animals; Dunnett's, *, p < 0.01). ERK1/2 activation was blocked in morphine-pretreated rats by coadministration of the MEK inhibitor U0126 (U/M; n = 22 neurons from three animals; Dunnett's, p > 0.05) compared with morphine alone (S/M). ERK1/2 activation was not increased in U0126-pretreated, saline-treated rats (U/S; n = 26 neurons from three animals; Dunnett's, p > 0.05). Each bar represents the mean intensity ± S.E.M. A to F, neurons in the vlPAG were labeled with phospho-ERK1/2 (A and D) and the neuron marker NeuN (B and E). Overlays of phospho-ERK1/2 and NeuN images (C and F) show that activation of ERK1/2 was specific to neurons (arrows). Increased phospho-ERK1/2 is observed in a representative slice from a rat treated chronically with morphine (A to C). Coadministration of U0126 and morphine prevented ERK1/2 phosphorylation (D to F). Scale bar = 20 μm. Rats were euthanized, and the brain was removed for immunohistochemical analysis of ERK1/2 phosphorylation 5 min after the last morphine injection on day 3.

Tara A. Macey, et al. J Pharmacol Exp Ther. 2009 November;331(2):412-418.

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