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 present study was to investigate the effects of intrahippocampal administration of N(omega)-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 microl) 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<.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 microl, P<.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.
Echeverry
Marcela B
MB
Department of Physiology, Medical School, Campus USP, SP, Ribeirão Preto, Brazil.
Guimarães
Francisco S
FS
Oliveira
Marina A
MA
do Prado
William A
WA
Del Bel
Elaine A
EA
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012149:Restraint, Physical; D013238:Stereotaxic Techniques; D013315:Stress, Psychological / Q000201:enzymology* / Q000523:psychology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester