Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects.
BACKGROUND
Systemic inhibition of neuronal nitric oxide synthase (nNOS) induces antidepressant-like effects in rodents. The mechanisms and brain regions mediating this effect are still unknown. The hippocampus is a brain region proposed to mediate adaptation to stress and antidepressant behavioral effects. Therefore, it could be involved in the antidepressant effects of NOS inhibitors.


OBJECTIVE
To test the hypothesis that nNOS inhibition in the dorsal hippocampus will induce antidepressant-like effects in the forced swimming test (FST) in rats.


METHODS
Rats implanted with cannulas aimed at the dorsal hippocampus were submitted to 15 min of forced swimming (pretest). Immediately before or after pretest they received bilateral microinjections of the nNOS inhibitor 7-nitroindazole (7-NI; 50, 100, or 200 nmol/0.5 microl) or vehicle, alone or combined with L-arginine. Additional groups received SIN-1 (125 or 250 nmol/0.5 microl), a NO donor, either before or after the pretest. Twenty-four hours later, immobility time was registered for 5 min in the FST.


RESULTS
7-NI (100 nmol) significantly decreased immobility time when administered either before or after pretest. Pretreatment with L-arginine (100 nmol/0.5 microl) prevented these effects but produced no significant effects per se. SIN-1 did not induce any significant effect.


CONCLUSIONS
These data suggest that the reduction of NO levels within the hippocampus can induce antidepressant-like effects; thus implicating endogenous hippocampal NO in the neurobiology of stress and depression.
Joca
Sâmia Regiane Lourenço
SR
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil. samia@usp.br
Guimarães
Francisco Silveira
FS
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007099:Imipramine / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D007191:Indazoles; D020030:Nitric Oxide Donors; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D052248:Nitric Oxide Synthase Type I; D007099:Imipramine; C080122:7-nitroindazole