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. 2021 Oct 5;10:e66048. doi: 10.7554/eLife.66048

Figure 6. Blocking ERK signaling pathway decreases the fraction of sensitized D1R SPN responses, leaves sensitized D2R SPN responses unaffected, and abolishes LS.

(A) Schematic overview of experimental setup. Animals are pre-treated with SL327 (30 mg/kg) 30 min before the first cocaine injection. Green squares indicate recording days (top) and 5-min recording windows (bottom). (B) Left panel: average distance travelled among recorded animals over different days. Paired student T-tests: day 8 vs day 1, p = 0.6, day 15 vs day 1, p = 0.02. Right panel: sensitization index on day 8 versus day 15. Spread shows S.E.M. Students T-test, p = 0.04, N = 8 mice. * = p < 0.05, n.s. = non significant. (C) Fraction of significantly responsive D1R and D2R neurons over days. D1R n = 205/192/185/181 neurons (day 0 /day 1 /day 8 /day 15) from 4 mice. Fishers Exact test: elevated activity: day 0 vs day 1: p = 1.6 x 10–2, day 8 vs day 15: p = 2.7 x 10–2, day 0 vs day 15: p = 5.2 x 10–4. Reduced activity: day 0 vs day 8: p = 1.4 x 10–2. All other comparisons p> 0.05. D2R n = 141/153/160/176 neurons (day 0 /day 1 /day 8 /day 15) from 4 mice. Fishers exact test, elevated activity: day 0 vs day 1: p = 3.4 x 10–3, reduced activity: day 0 vs day 8: p = 4.1 x 10–2, day 1 vs day 8: p = 4.5 x 10–2. All other intra-group comparisons p > 0.05. * = p < 0.05, ** = p < 0.01. S = saline, C = cocaine.

Figure 6.

Figure 6—figure supplement 1. Blocking ERK signaling pathway prevents D1R sensitization on day 8.

Figure 6—figure supplement 1.

Fraction of significantly responsive D1R neurons over days, with and without SL327 treatment (comparison of data presented in Figures 2D and 6C). D1R cocaine without SL327 n = 525/507/580 neurons from 7 mice. D1R cocaine with SL327 n = 205/192/185/185 neurons from 4 mice. Fishers Exact test: day 1, p = 0.15; day 8, p = 1.4 x 10–7. ** = p < 0.01. S = saline, C = cocaine, n.s. = non significant.