Effect of chlorpromazine on the localization of cAMP phosphodiesterase.

Chlorpromazine (CPZ) at dosages of 10 mg/kg body weight (b.wt.) affected the cytochemical localization of cAMP-dependent phosphodiesterase (cAMP PDE) activity in the synapses of the rat frontal cortex. Postsynaptic cAMP PDE activity was inhibited, and presynaptic activity increased. CPZ also inhibited membrane-bound ATPase activity in the frontal cortex. The activity of Na+-K+-ATPase was significantly (P less than 0.005) inhibited in isolated plasma membranes from the rat frontal cortex. CPZ exposure also affected the cytochemical localization of cations with potassium pyroantimonate. Precipitate, which could be removed with 5 mm EGTA, was decreased in the mitochondria and synaptic vesicles in presynaptic areas after CPZ treatment. The incorporation of 45Ca2+ into slices of the rat frontal cortex was also significantly (P less than 0.001) inhibited by CPZ. This ultrastructural study shows that CPZ may affect biochemical events in an opposite manner in the pre- and post-synaptic areas of some neurons of the frontal cortex.