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Delayed stress-induced antinociceptive effect of nitric oxide synthase inhibition in the dentate gyrus of rats

Stimulation of the hippocampal formation can modulate nociceptive mechanisms, whereas painful stimuli can activate this structure. Stress exposure can produce plastic changes in the hippocampus. Nitric oxide (NO) is an important neuroregulatory agent present in the hippocampus. The objective of the...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2002-12, Vol.74 (1), p.149-156
Main Authors: Echeverry, Marcela B, Guimarães, Francisco S, Oliveira, Marina A, do Prado, William A, Del Bel, Elaine A
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description Stimulation of the hippocampal formation can modulate nociceptive mechanisms, whereas painful stimuli can activate this structure. Stress exposure can produce plastic changes in the hippocampus. Nitric oxide (NO) is an important neuroregulatory agent present in the hippocampus. The objective of the present study was to investigate the effects of intrahippocampal administration of N ω-nitro- l-arginine methyl ester hydrochloride ( l-NAME), an inhibitor of NO synthase (NOS), on nociceptive processes in stressed and nonstressed rats. Male Wistar rats ( n=6–11/group) received unilateral microinjection of l-NAME (50–300 nmol/0.2 μl) into the dentate gyrus (DG) of the dorsal hippocampus. Immediately after the injection tail-flick reflex latency was measured. Stressed animals were submitted to 2 h of restraint and tested immediately or 1, 2, 5 or 10 days later. l-NAME failed to modify nociception in nonstressed rats. However, 5 days after, restraint l-NAME, at all doses tested, produced an antinociceptive effect (ANOVA, P
doi_str_mv 10.1016/S0091-3057(02)00964-4
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Stress exposure can produce plastic changes in the hippocampus. Nitric oxide (NO) is an important neuroregulatory agent present in the hippocampus. The objective of the present study was to investigate the effects of intrahippocampal administration of N ω-nitro- l-arginine methyl ester hydrochloride ( l-NAME), an inhibitor of NO synthase (NOS), on nociceptive processes in stressed and nonstressed rats. Male Wistar rats ( n=6–11/group) received unilateral microinjection of l-NAME (50–300 nmol/0.2 μl) into the dentate gyrus (DG) of the dorsal hippocampus. Immediately after the injection tail-flick reflex latency was measured. Stressed animals were submitted to 2 h of restraint and tested immediately or 1, 2, 5 or 10 days later. l-NAME failed to modify nociception in nonstressed rats. However, 5 days after, restraint l-NAME, at all doses tested, produced an antinociceptive effect (ANOVA, P&lt;.05). The dose–response curve had an inverted U shape. l-NAME antinociceptive effect was antagonized by previous treatment with l-arginine (150 nmol/0.2 μl, P&lt;.05). The results suggest that the modulation of nociceptive processes by NO in the dorsal hippocampus is dependent on previous stress exposure and on poststress interval.</description><subject>Analgesia</subject><subject>Animals</subject><subject>Antinociception</subject><subject>Biological and medical sciences</subject><subject>Dentate Gyrus - drug effects</subject><subject>Dentate Gyrus - enzymology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hippocampus</subject><subject>Male</subject><subject>Microinjections</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - physiology</subject><subject>Nitric Oxide Synthase - antagonists &amp; inhibitors</subject><subject>Nitric Oxide Synthase Type I</subject><subject>Pain Measurement - drug effects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reaction Time - drug effects</subject><subject>Restraint stress</subject><subject>Restraint, Physical</subject><subject>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. 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subjects Analgesia
Animals
Antinociception
Biological and medical sciences
Dentate Gyrus - drug effects
Dentate Gyrus - enzymology
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Hippocampus
Male
Microinjections
NG-Nitroarginine Methyl Ester - pharmacology
Nitric oxide
Nitric Oxide - physiology
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase Type I
Pain Measurement - drug effects
Rats
Rats, Wistar
Reaction Time - drug effects
Restraint stress
Restraint, Physical
Somesthesis and somesthetic pathways (proprioception, exteroception, nociception)
interoception
electrolocation. Sensory receptors
Stereotaxic Techniques
Stress, Psychological - enzymology
Stress, Psychological - psychology
Stress-induced analgesia
Tail-flick
Vertebrates: nervous system and sense organs
title Delayed stress-induced antinociceptive effect of nitric oxide synthase inhibition in the dentate gyrus of rats
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