DEPLETION OF NOS ACTIVITY IN THE RAT DENTATE GYRUS NEURONS BY DSP-4 AND PROTECTION BY DEPRENYL

DSP-4 is a potent and highly selective neurotoxin of noradrenergic axons of locus coeruleus origin. The authors found that in addition to depletion of the hippocampal noradrenergic terminals the histochemical reactivity of nitric oxide synthase (NOS, NADPH-diaphorase) was lost from neurons in the subgranule zone and hilar region of the dentate gyrus 2 weeks after a systemic administration of this toxin. Pretreatment with R(-)-deprenyl and 2-HxMP (2-hexyl-N-methylpropargylamine), which protects hippocampal noradrenergic axons against DSP-4 neurotoxicity, led to a complete prevention of the loss of NADPH-diaphorase activity.