7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Hölscher, Christian; McGlinchey, L; Anwyl, Roger; Rowan, Michael J.

doi:10.1101/lm.2.6.267

Cited by 99 publications

(75 citation statements)

References 51 publications

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“…In rat amygdala slice recordings, stimulation of guanylate cyclase by YC-1 leads to enhanced and enduring potentiation of the corticoamygdala pathway, and this potentiation could be eliminated by concomitant inhibition of NO synthase by L-NAME (Chien et al, 2003). Other studies have shown in vivo that inhibition of NO synthase impairs memory in rats as assessed by the Morris water maze (Holscher et al, 1996), and recently, Chien et al (2005) have tested YC-1 in vivo and found improvements in Morris water maze performance. Thus, if decreased long-term potentiation in the amygdala is responsible for the behavioral deficits in early separated monkeys, drug treatment with YC-1 may be a promising avenue for future therapeutic intervention.…”

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confidence: 99%

Amygdala Gene Expression Correlates of Social Behavior in Monkeys Experiencing Maternal Separation

Sabatini¹,

Ebert²,

Lewis³

et al. 2007

J. Neurosci.

113

132

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Children exposed to early parental loss from death or separation carry a greater risk for developing future psychiatric illnesses, such as major depression and anxiety. Monkeys experiencing maternal separation at 1 week of age show fewer social behaviors and an increase in self-comforting behaviors (e.g., thumb sucking) over development, whereas in contrast, monkeys experiencing maternal separation at 1 month of age show increased seeking of social comfort later in life. We sought to identify neural systems that may underlie these stress-induced behavioral changes by examining changes in mRNA content in amygdala tissue collected from 1 week separated, 1 month separated, and maternally reared infants at 3 months of age. mRNA from the right medial temporal lobe, primarily the amygdala, was analyzed using Affymetrix U133A 2.0 arrays. One gene, guanylate cyclase 1 ␣ 3 (GUCY1A3), showed differential expression between the 1 week and maternally reared groups and the 1 week and 1 month groups; these changes were confirmed by in situ hybridization. The expression of this gene was positively correlated with acute social-comforting behavior (r ϭ 0.923; p ϭ 0.001) and longer-term close social behavior (r ϭ 0.708; p ϭ 0.015) and negatively correlated with self-comforting behaviors (r ϭ Ϫ0.88; p Ͻ 0.001). Additional in situ hybridization studies of GUCY1A3 in normal monkeys showed that this gene is expressed at adult levels by 1 week of age and that its expression is greater in the amygdala than all other brain areas examined. We conclude that GUCY1A3 may contribute to the altered behavioral phenotypes that are differentially displayed depending on the age at which macaque infants experience an early-life stress.

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confidence: 99%

Amygdala Gene Expression Correlates of Social Behavior in Monkeys Experiencing Maternal Separation

Sabatini¹,

Ebert²,

Lewis³

et al. 2007

J. Neurosci.

113

132

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“…NOS inhibitors that are more selective for the neuronal isoform are not devoid of adverse effects and may decrease locomotion and/or motor coordination (Dzoljic et al, 1997;Harkin et al, 2003;Mutlu et al, 2011;Ulak et al, 2010;Volke et al, 2003). Moreover 7-NI seems to have a less favourable side-effect profile than TRIM in several paradigms that investigated learning and memory (Holscher et al, 1996;Mutlu et al, 2011;Yildiz Akar et al, 2009;Yildiz Akar et al, 2007;Zou et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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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“…It was noted, however, that the higher dose did in fact increase mean arterial blood pressure in these rats, indicating that eNOS may also have been inhibited by 7-NI. Administration of 30 mg/kg 7-NI to male rats 30 min prior to training impaired both working and reference memory for a spatial learning task (Hölscher et al 1995), although in another study, administration of either 25 or 50 mg/kg 7-NI to 2-mo-old male rats before training was found to impair only reference memory (Zou et al 1998). Finally, administration of 50 mg/kg 7-NI 1 h prior to passive avoidance training in 1-d-old chicks impaired recall when tested 30 min, 2 h, and 24 h (but not 5 min) later (Hölscher 1994).…”

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confidence: 99%

“…Administration of 30 mg/kg 7-NI to male rats 30 min prior to training impaired both working and reference memory for a spatial learning task (Hölscher et al 1995), although in another study, administration of either 25 or 50 mg/kg 7-NI to 2-mo-old male rats before training was found to impair only reference memory (Zou et al 1998). Finally, administration of 50 mg/kg 7-NI 1 h prior to passive avoidance training in 1-d-old chicks impaired recall when tested 30 min, 2 h, and 24 h (but not 5 min) later (Hölscher 1994). In the latter study, potential side effects of NOS inhibition on general performance (including motor skills and orientation) were excluded in separate experiments (see also Hölscher et al 1995).…”

mentioning

confidence: 99%

Hemispheric Dissociation of the Involvement of NOS Isoforms in Memory for Discriminated Avoidance in the Chick

Rickard¹,

Gibbs²

2003

Learn. Mem.

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Previous research has indicated a role for both the neuronal (nNOS) and endothelial (eNOS) nitric oxide isoforms in memory formation. In addition, two distinct periods of activity of nitric oxide activity, dissociated by hemispheric localization, are implicated following passive avoidance training in the chick. In the present study, we trained black Australorp-white Leghorn chicks on a color discrimination avoidance task. Diphenyleneiodonium chloride (1 μM) or N-propyl-l-arginine (50 μM) was administered into either the left or right hemisphere of the chick brain in an attempt to differentiate the effects of inhibiting eNOS or nNOS, respectively. The memory loss previously observed following administration of diphenyleneiodonium chloride between 10 and 20 min posttraining was found to be lateralized to the right hemisphere, although administration of this agent into the left hemisphere around the time of training was also amnestic. In contrast, N-propyl-l-arginine caused memory loss only when administered to the left hemisphere around the time of training. These findings suggest that activation of both eNOS and nNOS isoforms may be essential for long-term memory consolidation of this task. Further, these two periods of activity are defined temporally and by hemisphere localization, although confirmation with more selective inhibitors when they become available is advised

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7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Cited by 99 publications

References 51 publications

Amygdala Gene Expression Correlates of Social Behavior in Monkeys Experiencing Maternal Separation

Amygdala Gene Expression Correlates of Social Behavior in Monkeys Experiencing Maternal Separation

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

Hemispheric Dissociation of the Involvement of NOS Isoforms in Memory for Discriminated Avoidance in the Chick

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