Anti-psychotic drugs induce H3 phospho-acetylation in the nuclei of striatal neurons. (a–f) Coronal sections through dorsolateral striatum and adjacent cerebral cortex (a,b) were processed for H3pS10-acK14 immunoreactivity and stained with immunoperoxidase/ diaminobenzidine. Sections from an animal killed 120 min after a single dose of risperidone (a) or haloperidol (c,e) (1mg/kg). (b,d,f) Show sections from saline-treated controls. Notice increased numbers of dark stained nuclei in striatum (ST), but not cerebral cortex (CC) in risperidone-treated animal (a). Notice increased numbers of dark stained nuclei in striatum after haloperidol treatment (c,e). (g–i) Show digitized images from immunofluorescence-stained sections through dorsolateral striatum at 120 min after drug administration. Sections are triple-labeled, (g) shows NeuN immunopositive neuronal nuclei, (h) shows H3pS10-acK14 immunoreactivity and (i) 4,6,-diamidino-2-phenylindole dihydrochloride (DAPI) counterstain in order to identify nuclei. Arrows mark identical nuclei in corresponding images. Notice high levels of phospho-acetylated H3 in a subset of neuronal nuclei. (j, k) show higher resolution photomicrograph of neuronal nucleus. (j) DAPI stain, (k) H3pS10-acK14 immunolabeling. Notice compartmentalized distribution of H3pS10-acK14 in neuronal nucleus (k), with sparing of condensed chromatin (arrows) as defined by DAPI stain (j). Images taken at magnification (a,b) 4x10, 10x10 (c,d), 60x10 (e–i), 100x10 (j,k). Bar graph in (l) shows percentage of DAB/immunoperoxidase-stained nuclei (mean ± S.E.M.) expressing high H3pS10-acK14 immunoreactivity (operationally defined as > 7- fold increase above background) in dorso-lateral striatum of haloperidol-treated mice at 120 min after drug injection, in comparison to saline-treated controls. (m) Shows fraction of NeuN+ positive nuclei expressing high H3pS10-acK14 immunofluorescence >7x background. *p < 0.05. Notice significant increase in H3pS10-acK14 immunoreactivity in neuronal nuclei of haloperidol-treated animals.