Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice

Silva, Gisele de Lourdes da; Matteussi, Andreza S.; Santos, Adair R.S.; Calixto, João Β.; Rodrigues, Ana Lúcia S.

doi:10.1097/00001756-200011270-00022

Cited by 110 publications

(62 citation statements)

References 16 publications

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“…NOS inhibitors have been reported to reduce immobility time acutely in the TST and FST in mice (da Silva et al, 2000;Ghasemi et al, 2008;Harkin et al, 2004;Harkin et al, 1999;Rosa et al, 2003;Volke et al, 2003). However, to our knowledge, there are no reports on delayed or sustained effects of NOS inhibitors in these paradigms following a single dose.…”

Section: Discussionmentioning

confidence: 92%

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Doucet

Levine

Dev

et al. 2013

Neuropsychopharmacol

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Previous studies have demonstrated that nitric oxide (NO) synthase inhibitors are as efficacious as tricyclic antidepressants in preclinical antidepressant screening procedures and in attenuating behavioural deficits associated with animal models of depression. The N-methyl-D-aspartate receptor (NMDA-R) complex gates Ca 2 þ , which interacts with calmodulin to subsequently activate NO synthase. We hypothesised that uncoupling neuronal nitric oxide synthase (nNOS) from the NMDA-R through the scaffolding protein postsynaptic density protein 95 (PSD-95) would produce behavioural antidepressant effects similar to NO synthase inhibitors. Small-molecule inhibitors of the PSD-95/nNOS interaction, IC87201 (0.01-2 mg/kg) and ZL006 (10 mg/kg) were tested for antidepressant properties in tests of antidepressant activity namely the tail suspension and forced swim tests in mice. We now report that IC87201 and ZL006 produce antidepressant-like responses in the forced swimming test (FST) and tail suspension test (TST) following a single administration in mice. By contrast to the tricyclic antidepressant imipramine (25 mg/kg), the effects are not observed 1 h following drug administration but are apparent 24 and 72 h later. Furthermore prior exposure to the TST or FST is required in order to observe the antidepressantrelated activity. Similar delayed and sustained antidepressant-like effects were observed following TRIM (50 mg/kg) and ketamine (30 mg/kg) in the TST. The antidepressant-like effects of ZL006 also generalise to IC87201 in the TST. IC87201 was devoid of effects on locomotor activity and step-through latency in the passive avoidance cognition test. These data support the hypothesis that targeting the PSD-95/nNOS interaction downstream of NMDA-R produces antidepressant effects and may represent a novel class of therapeutics for major depressive disorders.

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Section: Discussionmentioning

confidence: 92%

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Doucet

Levine

Dev

et al. 2013

Neuropsychopharmacol

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“…To date a number of studies have demonstrated that inhibition of nitric oxide synthase (NOS) produces anxiolytic and antidepressant-like behavioural effects in a variety of animal paradigms (da Silva et al 2000;Harkin et al 1999;Jeffreys and Funder, 1996;Mutlu et al, 2009;Spiacci et al, 2008;Spolidório et al, 2007;Ulak et al, 2008;Yildiz et al 2000a,b). Previously we reported that the NOS inhibitors, N G -nitro-L-arginine (L-NA) and 7-nitroindazole (7-NI), dose dependently reduce immobility and increase swimming behaviour in the rat and mouse forced swimming test (FST), a test predictive of antidepressant activity (Harkin et al, 1999(Harkin et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test

Gigliucci

Buckley

Nunan

et al. 2010

Pharmacology Biochemistry and Behavior

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“…Accordingly, a rapidly increasing body of evidence coming from pharmacological studies in animals argues in favour of this hypothesis. [26][27][28][29][30][31][32][33][34][35] Finally, a landmark study by Akbarian et al, 36,37 followed by further histopathological investigations, 38 argues that nitrinergic neurons are pathologically altered in SCZ.…”

Section: Introductionmentioning

confidence: 99%

A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function

et al. 2006

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Nitric oxide (NO) is a gaseous neurotransmitter thought to play important roles in several behavioral domains. On a neurobiological level, NO acts as the second messenger of the Nmethyl-D-aspartate receptor and interacts with both the dopaminergic as well as the serotonergic system. Thus, NO is a promising candidate molecule in the pathogenesis of endogenous psychoses and a potential target in their treatment. Furthermore, the chromosomal locus of the gene for the NO-producing enzyme NOS-I, 12q24.2, represents a major linkage hot spot for schizophrenic and bipolar disorder. To investigate whether the gene encoding NOS-I (NOS1) conveys to the genetic risk for those diseases, five NOS1 polymorphisms as well as a NOS1 mini-haplotype, consisting of two functional polymorphisms located in the transcriptional control region of NOS1, were examined in 195 chronic schizophrenic, 72 bipolar-I patients and 286 controls. Single-marker association analysis showed that the exon 1c promoter polymorphism was linked to schizophrenia (SCZ), whereas synonymous coding region polymorphisms were not associated with disease. Long promoter alleles of the repeat polymorphism were associated with less severe psychopathology. Analysis of the mini-haplotype also revealed a significant association with SCZ. Mutational screening did not detect novel exonic polymorphisms in patients, suggesting that regulatory rather than coding variants convey the genetic risk on psychosis. Finally, promoter polymorphisms impacted on prefrontal functioning as assessed by neuropsychological testing and electrophysiological parameters elicited by a Go-Nogo paradigm in 48 patients (continuous performance test). Collectively these findings suggest that regulatory polymorphisms of NOS1 contribute to the genetic risk for SCZ, and modulate prefrontal brain functioning.

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Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice

Cited by 110 publications

References 16 publications

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test

A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function

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