Serotonin depletion in rat hippocampus attenuates L-NAME-induced spatial learning deficits

Brain Res. 2003 Feb 14;963(1-2):244-51. doi: 10.1016/s0006-8993(02)03987-2.

Abstract

Inhibition of nitric oxide (NO) synthesis has been found to produce learning deficits in spatial tasks. Recent studies also suggest a regulatory effect of endogenous NO on hippocampal serotonin (5-HT) release and have shown that NO-synthase (NOS) inhibitors increased extracellular levels of serotonin (5-HT) in the rat hippocampus. To clarify possible interactions between NO and 5-HT in the hippocampus on learning processes, the effect of selective hippocampal 5-HT depletion on NOS inhibition-induced spatial learning deficits was investigated. Rats received bilateral injections of 5,7-dihydroxytryptamine (5,7-DHT), a 5-HT neurotoxin, or its vehicle in the CA1 region of hippocampus following pretreatment with desipramine. Rats were subjected to 5 days of training in the Morris water maze (MWM); 4 days with the invisible platform to test spatial learning and the 5th day with the visible platform to test motivation and sensorimotor coordination. Nomega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, was administered to either sham-operated or 5,7-DHT-lesioned groups 30 min before training each day. Results showed that L-NAME significantly impaired the ability of rats to locate the hidden platform. This impairment was reversed by co-administration of mole equivalent dose of L-arginine, the NO precursor. Although the 5,7-DHT-induced lesion had no effect by itself on rat performance in the MWM, it attenuated the memory impairment caused by L-NAME. The observed effect suggests an interaction between NO and 5-HT in the hippocampus on spatial memory formation; however, the mechanism of interaction is still unclear and requires further investigation.

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Arginine / pharmacology
  • Desipramine / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Hippocampus / physiology*
  • Male
  • Maze Learning / drug effects*
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Neurotoxins / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I
  • Rats
  • Rats, Wistar
  • Serotonin / physiology*

Substances

  • Adrenergic Uptake Inhibitors
  • Enzyme Inhibitors
  • Neurotoxins
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Arginine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Desipramine
  • NG-Nitroarginine Methyl Ester