The type IV-specific phosphodiesterase inhibitor rolipram and its effect on hippocampal long-term potentiation and synaptic tagging.
We investigated the effects of rolipram, a selective cAMP phosphodiesterase (PDE) inhibitor, on late plastic events during functional CA1 plasticity in vitro in rat hippocampal slices. We present data showing that an early form of long-term potentiation (LTP) (early-LTP) that normally decays within 2-3 hr can be converted to a lasting LTP (late-LTP) if rolipram is applied during tetanization. This rolipram-reinforced LTP (RLTP) was NMDA receptor and protein synthesis dependent. cAMP formation in region CA1 during late-LTP requires dopaminergic receptor activity (Frey et al., 1989, 1990). Thus, we studied whether RLTP was influenced by inhibitors of the D(1)/D(5) receptor. Application of the specific D(1)/D(5) antagonist SCH23390 (0.1 microm) did not prevent RLTP, suggesting that the phosphodiesterase inhibitor acts downstream of the D(1)/D(5) receptors. We also studied whether rolipram can interact with processes of synaptic tagging, because RLTP was also dependent on protein synthesis, similar to late-LTP. Inhibition of PDE and subsequent induction of RLTP in one synaptic population were able to transform early-LTP into late-LTP in a second, independent synaptic population of the same neurons. This supports our hypothesis that cAMP-dependent processes are directly involved in the synthesis of plasticity-related proteins.
Navakkode
Sheeja
S
Leibniz Institute for Neurobiology, Department of Neurophysiology, D-39118 Magdeburg, Germany.
Sajikumar
Sreedharan
S
Frey
Julietta Uta
JU
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D018492:Dopamine Antagonists / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D050641:Receptors, Dopamine D5; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D020889:Rolipram / Q000494:pharmacology*; D013746:Tetany / Q000503:physiopathology
D001552:Benzazepines; D018492:Dopamine Antagonists; C493607:Drd5 protein, rat; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D050641:Receptors, Dopamine D5; D000841:Anisomycin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D004640:Emetine