Fig. 5.
D2-like antagonists induce striatal H3 phospho-acetylation by activating cAMP-dependent PKA. (a, b) Immunoblots from left (L) and right (R) striatum of rats showing H3pS10-acK14 and H4acK12 immunoreactivity, and gel coomassie blue stain as additional loading control. Animals shown in (a) received PBS or Rp-cAMPs into the left striatum, followed 30 min later by a systemic dose of haloperidol or saline. Blots show striatal histones at 30 min after the systemic treatment. Notice robust increase in H3pS10-acK14 in left and right striatum of haloperidol-treated animals that received PBS into the left striatum. Notice attenuated response in left striatum of haloperidol-treated animals that received Rp-cAMPs into the left striatum. (b) Striatal immunoblots from animals 60 min after an infusion of PBS or Sp-cAMPs into the left striatum. There is a robust increase in H3pS10-acK14 in left striatum of Sp-cAMPs treated animals. (c) Blots from primary striatal cultures, treated with vehicle, forskolin or H89 followed by forskolin. Note increased levels of H3pS10-acK14 in forskolin-treated cultures that is completely blocked by H89. The cultures were treated with forskolin for a period of 30 min with or without pre-treatment with H89 for 30 min; pre-treatment with H89 was for 30 minutes. (d) Levels of H3pS10-acK14 immunoreactivity (mean ± S.E.M.) of in vivo experiments with cAMP analogue drugs. Gray bar, left striatum; checkered bar, right striatum. Notice that Rp-cAMPs induced a significant decrease in left striatum of haloperidol-treated animals, while Sp-cAMPs induced a significant increase from baseline. *= p < 0.05. (e) Graph summarizing levels of H3pS10-acK14 immunoreactivity (mean ± S.E.M.) of In vitro experiments, notice significant increase from baseline in forskolin-treated cultures and significance decrease from baseline when cultures were pre-treated with H89.