Blockade of norepinephrine-induced long-lasting potentiation in the hippocampal dentate gyrus by an inhibitor of protein synthesis.
The mechanism of action of norepinephrine (NE)-induced potentiation of the population spike in the dentate gyrus of hippocampal slices was examined and compared with NE effects in field CA1. NE-induced potentiation was confined to the dentate gyrus, where slices perfused for 30 min with concentrations of NE as low as 5 microM exhibited potentiation of the perforant path evoked population spike. Potentiation began within 15 min, and lasted many hours after NE was washed out. Experiments where slices were pre-incubated with the protein synthesis inhibitor emetine indicated that there are two distinct phases to NE-induced potentiation. The initial short-term NE-induced potentiation (NEP) seen during NE application was not affected by a 30 min pre-incubation with emetine, whereas the long-lasting potentiation (NELLP) which persists after NE washout was completely blocked by emetine at a concentration which we have previously shown to be effective in blocking hippocampal long-term potentiation (LTP). Additional experiments indicated that both phases of NE-induced potentiation were completely blocked by the beta-antagonist propranolol and the beta 1-antagonist metoprolol. Furthermore, pre-incubation of slices with the direct-acting adenylate cyclase stimulant forskolin shifted the dose-response curves for both phases of NE-induced potentiation to the left. These results suggest that NE-induced potentiation is probably mediated by beta 1-receptor stimulation of adenylate cyclase. We have previously shown an importance for beta 1-receptor stimulation of adenylate cyclase in the production of LTP in the dentate. Thus, these results demonstrate a number of similarities between hippocampal LTP and NELLP in the dentate gyrus.
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D004553:Electric Conductivity / Q000187:drug effects; D004640:Emetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005576:Colforsin; D009638:Norepinephrine; D004640:Emetine