GALANIN STIMULATES THE N-METHYL-D-ASPARTATE RECEPTOR NITRIC-OXIDE CYCLIC-GMP PATHWAY IN-VIVO IN THE RAT VENTRAL HIPPOCAMPUS

We investigated whether the neuropeptide galanin affects the nitric ox ide synthase/cyclic GMP pathway in rat hippocampus by measuring in viv o the extracellular cyclic GMP levels during microdialysis. Galanin (2 .5 and 3.5 nmol) i.c.v.) dose-dependently raised the extracellular lev els of cyclic GMP in the ventral but not the dorsal hippocampus. The e ffect of 3.5 nmol galanin was blocked by local application of tetrode toxin and inhibited by the high-affinity galanin antagonist M40 (galan in-[1-12]-Pro(3)-[Ala-Leu](2)-Ala amide). The non-competitive iv-methy l-D-aspartate receptor antagonist dizocilpine maleate (30 mu M infused into the ventral hippocampus or 0.2 mg/kg, i.p.) and the competitive one, 3-([R]-carboxypiperazin-4-yl)-propyl-phosphonic acid (50 mu M inf used), but not local perfusion of the AMPA antagonist 6-nitro-7-sulpha moylbenzo(f)quinoxaline-2,3-dione (15 mu M) abolished the galanin-evok ed cyclic GMP response in the hippocampus. Inhibitors of nitric oxide synthase, L-Arg(NO2)-OMe . HCl and 7-nitroindazole monosodium salt, ap plied locally, blocked the galanin-induced increase in hippocampal ext racellular cyclic GMP. This increase was also prevented by local appli cation of 1H-(1,2,4)oxadiazolo(4,3a) quinoxalin-1-one, a selective inh ibitor of soluble guanylyl cyclase. The galanin receptors mediating th e rise in cyclic GMP reside outside the hippocampus, as galanin (0.35- 3 nmol) locally applied had no effect. The results provide in vivo evi dence that galanin stimulates the iv-methyl-D-aspartate receptor/nitri c oxide synthase/cyclic GMP pathway in the ventral hippocampus, which may be of importance in memory processes. (C) 1998 IBRO. Published by Elsevier Science Ltd.