Fig. 4: Heroin leads to enhanced chromatin accessibility, transcription, and activity of FYN.
a, b ATAC-seq signal over a 600 bp region (chr6:112194332–112194931) overlapping the transcription start site of FYN in NeuN-positive neuronal (a) and NeuN-negative non-neuronal (b) cell populations. Accessibility of this region is markedly increased by heroin, especially in neuronal cells. c FYN mRNA levels were increased in the putamen of human heroin users compared to matched controls (n = 30 heroin users, n = 16 controls, Student’s t-test, t44 = 1.859, p = 0.0349). d Fyn mRNA levels were increased in the caudate-putamen of heroin self-administering rats (n = 12/28 control/heroin, Student’s t-test, t37 = 2.305, p = 0.0269). e Fyn mRNA levels were increased in primary striatal cells treated with morphine (one-way ANOVA F2,13 = 6.419, p = 0.0115; significant increase observed with 100 µM morphine, Student’s t-test t10 = 3.785, p = 0.0036). f Active p(Y418)-Fyn levels were increased in the dorsal striatum of heroin self-administering rats 24 h after the last session (n = 8/12 control/heroin, Student’s t-test, t18 = 2.563, p = 0.0196). g Inactive p(Y529)-Fyn levels were decreased in the same animals (n = 8/12 control/heroin, Student’s t-test, t18 = 2.411, p = 0.0268). h Ratio of active/inactive p-Fyn was significantly increased in the same animals (n = 8/12 control/heroin, Student’s t-test, t18 = 3.037, p = 0.0071). i, j Active (I; linear regression, F1,18 = 5.854, r = 0.50, p = 0.0263) but not inactive (J; linear regression, F1,18 = 0.4255, r = −0.15, p = 0.5225) dorsal striatal p-Fyn correlated positively with active lever pressing. k Active p(Y418)-Fyn levels were increased in the dorsal striatum of heroin self-administering rats 2 weeks after the last session (n = 8/group, Student’s t-test, t14 = 2.403, p = 0.0307). l Inactive p(Y529)-Fyn levels were decreased in the same animals (n = 8/group, Student’s t-test, t14 = 2.265, p = 0.0399). m Ratio of active/inactive p-Fyn was significantly increased in the same animals (n = 8/group, Student’s t-test, t14 = 3.106, p = 0.0077). n Active p(Y418)-Fyn levels showed an increasing trend (n = 8/group, Student’s t-test, t14 = 1.918, p = 0.0757) in the dorsal striatum of naive rats injected with a single dose of 1 mg/kg heroin. o Inactive p(Y529)-Fyn levels showed a decreasing trend in the same animals (n = 8/group, Student’s t-test, t14 = 2.032, p = 0.0616). p Ratio of active/inactive p-Fyn was increased in the same animals (n = 8/group, Student’s t-test, t14 = 2.492, p = 0.0259). Data are represented as mean ± SEM (normalized to saline group in f–p). Source data are provided as a Source Data file.
