Protective effect of 7-nitroindazole against DSP-4 induced noradrenaline depletion in mouse hippocampus

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a selective noradre naline (NA) uptake blocker, capable of inducing a longlasting depletion of NA in some noradrenergic axon terminals originating from the locus coeruleu s in rodents. Pretreatment with 7-nitroindazole, a fairly selective inhibit or of neuronal nitric oxide synthase in vivo, partially prevented DSP-4 ind uced NA depletion in mouse hippocampus measured seven days after the neurot oxic insult. Administration of L-arginine, the substrate of nitric oxide sy nthase, altered neither the NA depletion induced by DSP-4, nor the protecti ve effect of 7-nitroindazole. Inhibition of nitric oxide synthesis by N(G)- nitro-L-arginine methyl ester did not attenuate the NA depleting effect of DSP-LC. Thus, the contribution of neuronal nitric oxide synthase inhibition to the protective effect of 7-nitroindazole needs further studies. As 7-ni troindazole did not block NA uptake, this cannot play a part in the protect ive effect. The possible contribution of monoamine oxidase B enzyme inhibit ion by 7-nitroindazole to the protective effect is also discussed.