DOSE AND TIME DEPENDENCY OF ANGIOTENSIN-II INHIBITION OF HIPPOCAMPAL LONG-TERM POTENTIATION

We previously reported that injection of 1.0 mu l of 4.78 mu M angiotensin II (AII) above the hippocampus in rats inhibits long-term potentiation (LTP) induction in medial perforant path-stimulated dentate granule cells. The present experiments were conducted in urethane-anesthetized Sprague-Dawley rats. LTP was measured in terms of the relative change in slope of the population EPSP compared to baseline. Effects of 0.48, 0.956, 1.195, 2.39, and 4.78 mu M AII and time delays of 30, 60, 90, and 150 min with the 4.78 mu M dose were determined. Results were significant and demonstrate that AII inhibition of LTP in dentate granule cells is both dose and time dependent. The threshold is approximately 1.0 pmol of peptide. Inhibition due to the 4.78 mu M AII begins slowly after 1 h and is complete over the next 30 min, continues for another 30 min, and then fully recovers by the end of the next 30 min. This time dependency could be due to the internalization of the AII, interaction with a cytosolic receptor, and eventual degradation.