TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION OF PHOSPHODIESTERASE TYPE-IV ISOZYMES IN RAT-BRAIN BY ELECTROCONVULSIVE SEIZURE AND ANTIDEPRESSANT DRUG-TREATMENT

We examined the influence of electroconvulsive seizure (ECS) and imipr amine (IMI) treatment on the transcription and translation of cyclic n ucleotide phosphodiesterase type IV (PDE IV) isozymes in the rat brain . Our in situ hybridization studies revealed an increase of PDE IV-B m RNA level in various brain regions after acute ECS, However, the incre ase of PDE IV activity was produced not by acute but by chronic ECS tr eatment in the frontal cortex. Increased PDE IV-B mRNA expression in f rontal but not in hippocampal subfields was induced also after chronic ECS treatment. Although an increase in PDE IV-A mRNA expression of th e dentate gyrus in the hippocampus was observed, no change of PDE IV a ctivity was produced in the hippocampus by acute or chronic ECS treatm ent. These results suggest that the repeated increases of PDE IV-B mRN A expression are attributable to the increase of PDE IV translation. I ncreased PDE IV-B transcription and PDE IV translation in the frontal cortex were also produced after chronic IMI treatment. This is the fir st report demonstrating an expressional regulation of Drosophila melan ogaster dunce (dnc) gene homologue PDE IV isozymes in the brain. Altho ugh no pathophysiological conditions with reduced PDE IV activity in t he nervous system are known except for a learning deficit in the mutan t fly dnc(-), our results suggest possible treatments to cope with red uced PDE IV activity.