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[Preprint]. 2024 Nov 7:2024.11.06.622304. [Version 1] doi: 10.1101/2024.11.06.622304

Figure 1. Morphine exposure from P1 – P14 is sufficient to induce opioid withdrawal traits in FVB/N pups.

Figure 1.

Data are plotted as the mean ± SEM. Closed circles = females. Open circles = males. Data were analyzed using linear mixed models with Saline Treatment, Female Sex, and NCrl Substrain as the reference variables and Pup as a random effect (for repeated measures). A. Experimental Timeline. B. Body Weight: The effect of Morphine Treatment on body weight was dependent on Postnatal Day (β = −0.29, SE = 0.012, t(166) = −24.14, ****p < 0.0001), where morphine-withdrawn pups weighed significantly less than saline-control pups from P2 – P14 (P2: **p = 0.0027; P3 – P14: ****p < 0.0001). C. Temperature: There were main effects of Morphine Treatment (β = −1.98, SE = 0.30, t(475) = −6.65, ****p < 0.0001) and Postnatal Day (β = 0.65, SE = 0.041, t(2182) = 15.97, ****p < 0.0001), but no interaction (β = 0.00042, SE = 0.026, t(2181) = 0.016, p = 0.99). SAL, n = 84; MOR, n = 84. D. P7 Hot Plate Latency: There were no interactions (all p ≥ 0.11). Morphine pups displayed decreased hot plate latency compared to saline-control pups (β = −13.03, SE = 0.95, t(177) = −13.70, ****p < 0.0001). SAL, n = 90 (52F, 38M); MOR, n = 89 (43F, 46M). E. P7 Hot Plate Velocity: There were no interactions (all p ≥ 0.91). There was no effect of Morphine Treatment on hot plate velocity (β = −0.00072, SE = 0.0026, t(158) = −0.28, p = 0.78). SAL, n = 83 (48F, 35M) ; MOR, n = 79 (39F, 40M) . F. P7 Tail Withdrawal Latency: There were no interactions (all p ≥ 0.15). Morphine-withdrawn pups displayed reduced tail withdrawal latencies compared to saline-control pups (β = −0.76, SE = 0.34, t(173) = −2.25, *p = 0.026). SAL, n = 77 (44F, 33M); MOR, n = 86 (41F, 45M). G. P14 Hot Plate Latency: There were no interactions (all p ≥ 0.29). Morphine-withdrawn pups displayed reduced hot plate latencies compared to saline-control pups (β = −10.82, SE = 2.14, t(157) = −5.053, ****p < 0.0001). SAL, n = 83 (48F, 35M; MOR, n = 75 (36F, 39M). H. P14 Hot Plate Velocity: There were no interactions (all p ≥ 0.63). Morphine-withdrawn pups displayed increased hot plate velocity compared to saline-control pups (β = 0.0033, SE = 0.0017, t(158) = 1.99, *p = 0.049). SAL, n = 83 (47F, 36M); MOR, n = 77 (37F, 40M). I. P14 Tail Withdrawal Latency: There were no interactions (all p ≥ 0.18). There was no effect of Morphine Treatment on tail withdrawal latency (β = −0.32, SE = 0.21, t(164) = −1.47, p = 0.14). SAL, n = 82 (48F, 34M); MOR, n = 75 (35F, 40M).