title: Angiotensin-(1-7)-induced plasticity changes in the lateral amygdala are mediated by COX-2 and NO.
abstract: It is known from studies outside the brain that upon binding to its receptor, angiotensin-(1-7) elicits the release of prostanoids and nitric oxide (NO). Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to prostaglandins. Since there are no data available so far on the role of COX-2 in the amygdala, in a first step we demonstrated that the selective COX-2 inhibitor NS-398 significantly reduced the probability of long-term potentiation (LTP) induction in the lateral nucleus of the amygdala. Similarly, in COX-2(-/-) mice, LTP induced by external capsule (EC) stimulation was impaired. Second, we evaluated the action of angiotensin-(1-7) in the amygdala. In wild-type mice, angiotensin-(1-7) increased LTP. This LTP-enhancing effect of Ang-(1-7) was not observed in COX-2(+/-) mice. However, in COX-2(-/-) mice, Ang-(1-7) caused an enhancement of LTP similar to that in wild-type mice. The NO synthetase inhibitor L-NAME blocked this angiotensin-(1-7)-induced increase in LTP in COX-2(-/-) mice. Low-frequency stimulation of external capsule fibers did not cause long-term depression (LTD) in drug-free and angiotensin-(1-7)-treated brain slices in wild-type mice. In contrast, in COX-2(-/-) mice, angiotensin-(1-7) caused stable LTD. Increasing NO concentration by the NO-donor SNAP also caused LTD in wild-type mice. Our study shows for the first time that LTP in the amygdala is dependent on COX-2 activity. Moreover, COX-2 is involved in the mediation of angiotensin-(1-7) effects on LTP. Finally, it is recognized that there is a molecular cross-talk between COX-2 and NO that may regulate synaptic plasticity.
authors.affiliation: Institute of Neurophysiology, Charité-Universitätsklinikum Berlin, Berlin, Germany. doris.albrecht@charite.de
authors.forename: Doris
authors.initials: D
authors.lastname: Albrecht
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006579:Heterozygote; D006720:Homozygote; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009578:Nitrobenzenes / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009578:Nitrobenzenes; D010446:Peptide Fragments; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester