Hippocampal nNOS inhibition induces an antidepressant-like effect:involvement of 5HT1A receptors

Autor: Vinicius A. Hiroaki-Sato, Sâmia R.L. Joca, Amanda J. Sales, Caroline Biojone
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Pyridines
Nitric Oxide Synthase Type I
Hippocampal formation
Pharmacology
Swimming/psychology
Serotonergic
Arginine
Hippocampus
Piperazines
Nitric oxide
chemistry.chemical_compound
Fluoxetine
Stress
Psychological/drug therapy

Serotonin Antagonists/pharmacology
Animals
Hippocampus/drug effects
Enzyme Inhibitors
Piperazines/pharmacology
Rats
Wistar

Receptor
Receptor
Serotonin
5-HT1A/metabolism

Swimming
Enzyme Inhibitors/pharmacology
Pyridines/pharmacology
Antagonist
Fluoxetine/pharmacology
Nitric Oxide Synthase Type I/metabolism
Antidepressive Agents
Rats
Psychiatry and Mental health
Disease Models
Animal

chemistry
Antidepressive Agents/pharmacology
Receptor
Serotonin
5-HT1A

Exploratory Behavior
Arginine/analogs & derivatives
Antidepressant
Exploratory Behavior/drug effects
Serotonin
Serotonin Antagonists
Stress
Psychological

Behavioural despair test
Zdroj: Hiroaki-Sato, V A, Sales, A J, Biojone, C & Joca, S R L 2014, ' Hippocampal nNOS inhibition induces an antidepressant-like effect : involvement of 5HT1A receptors ', Behavioural Pharmacology, vol. 25, no. 3, pp. 187-96 . https://doi.org/10.1097/FBP.0000000000000035
DOI: 10.1097/FBP.0000000000000035
Popis: Systemic as well as hippocampal administration of nNOS inhibitors induces antidepressant-like effects in animal models. However, the mechanisms underlying these effects have not been completely understood. Evidence has suggested that nNOS inhibition increases serotonin signaling in the brain. Moreover, activation of prosencephalic 5HT1A receptors is considered to mediate stress coping and antidepressant effects. On this basis, the aim of this study was to investigate the hypothesis that the antidepressant-like effect induced by nNOS inhibition in the dorsal hippocampus (DH) would involve local serotonergic signaling and 5HT1A receptor activation. Therefore, rats were subjected to the forced swimming test and received microinjections of fluoxetine, NPA (Nω-propyl-L-arginine, selective nNOS inhibitor), WAY100635 (5HT1A antagonist), and vehicle, alone or in combination, into the DH. Exposure to the forced swimming test increased nitric oxide acid levels in the DH. The administration of NPA or fluoxetine in the DH induced dose-dependent antidepressant-like effects. WAY100635 microinjection in the DH did not induce any effect per se, but it counteracted NPA-induced and fluoxetine-induced effects. These results suggest that the antidepressant-like effect induced by the administration of nNOS inhibitors in the DH involves local serotonergic signaling and 5HT1A receptor activation.
Databáze: OpenAIRE