Serotonin depletion in rat hippocampus attenuates L-NAME-induced spatial learning deficits.
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.
Majlessi
Nahid
N
Department of Physiology and Pharmacology, Pasteur Institute of Iran, Pasteur Ave., 13164, Tehran, Iran. nahidm@institute.pasteur.ac.ir
Kadkhodaee
Mehri
M
Parviz
Mohsen
M
Naghdi
Nasser
N
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*
D018759:Adrenergic Uptake Inhibitors; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D003891:Desipramine; D019331:NG-Nitroarginine Methyl Ester