Selective and nonselective neuronal NOS inhibitors impair cognitive function in the three panel runway and passive avoidance tasks in rats

Utkan, Tijen; Göçmez, S.S.; Özer, Cüneyt; Gacar, Nejat; Arıcıoğlu, Feyza

doi:10.1016/j.pbb.2012.02.020

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Many studies have investigated TWAA and PA response in rats using NOS inhibitors and NO donors/precursors (Chien et al., 2008; Komsuoglu-Celikyurt et al., 2011; Kucukatay et al, 2009; Pitsikas et al, 2001; Utkan, Gocmez, Ozer, Gacar, & Aricioglu, 2012). Majority of these studies were carried out by administration of non-selective and putative partially selective NOS1 inhibitors and NO donors/precursors.…”

Section: Discussionmentioning

confidence: 99%

Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice.

Gao¹,

Heldt²

2015

Behavioral Neuroscience

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Nitric oxide (NO) is an important molecule for the proper development and function of the central nervous system. In this study, we investigated the behavioral alterations in the neuronal nitric oxide synthase knockout mice (NOS1 KO) with a deficient NO production mechanism in the brain, characterizing it as a potential rodent model for attention deficit / hyperactivity disorder (ADHD). NOS1 KO exhibited higher locomotor activity than their wildtype counterparts in a novel environment, as measured by open field (OF) test. In a two-way active avoidance paradigm (TWAA), we found sex-dependent effects, where male KO displayed deficits in avoidance and escape behavior, sustained higher incidences of shuttle crossings and higher incidences of inter-trial interval crossings, suggesting learning and/or performance impairments. On the other hand, female KO demonstrated few deficits in TWAA. Molsidomine (MSD), a NO donor, rescued TWAA deficits in male KO when acutely administered before training. In a passive avoidance paradigm, KO of both sexes displayed significantly shorter step-through latencies after training. Further, abnormal spontaneous motor activity rhythms were found in the KO during the dark phase of the day, indicating dysregulation of rhythmic activities. These data indicate that NOS1 KO mimic certain ADHD-like behaviors and could potentially serve as a novel rodent model for ADHD.

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Section: Discussionmentioning

confidence: 99%

Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice.

Gao¹,

Heldt²

2015

Behavioral Neuroscience

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“…The nNOS isoform has been pointed as the major NOS isoform that is essentially involved with enhancement of memory formation and consolidation [56,57], although eNOS has been also indicated to participate in processes of memory formation [58]. Although the nNOS activity in the hippocampus is a key factor for learning and memory processes, Rappanelli et al [59] showed that both eNOS and nNOS activities in the prefrontal cortex and hippocampus were augmented during the operant learning process in rats.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, exposures to uncontrollable or severe stressors induced nNOS expression in brain structures including the hippocampus, amygdala and cortex [59] and there is evidence indicating that increased production of NO in the dorsolateral periaqueductal gray area is involved in the anxiety behavior displayed by rats [60]. Additionally, both nNOS and iNOS participate of mechanisms related with neurogenesis in the hippocampus, since decreases in nNOS activity or increases in iNOS expression have been reported to promote neurogenesis in the dentate gyrus [57-60]. Besides, it is assumed that there is an inverse relation between increases in the systemic expression of iNOS and the amount of encephalic nNOS [61], although the mechanism regulating this relation still needs better comprehension.…”

Section: Discussionmentioning

confidence: 99%

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

Machado-Nils

Faria

Vieira

et al. 2013

J Circadian Rhythms

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BackgroundNitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons.ResultsAdult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase.ConclusionsThe data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms.

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“…PA task (model 7551, Ugo Basile, Italy) was utilized for the assessment of emotional memory based on contextual fear conditioning, as previously described [32]. Briefly, rats learn to avoid a specific place associated with an aversive event.…”

Section: Pa Testmentioning

confidence: 99%

“…A water tank (150 cm in diameter) was used to measure spatial memory as previously described [32]. The platform was put in the centre of the southwest quadrant and submerged 1.5 cm below the surface of water, and a small black plastic ball was put on the water surface.…”

Section: Mwm Testmentioning

confidence: 99%

Role of the nitric oxide-soluble guanylyl cyclase pathway in cognitive deficits in streptozotocin-induced diabetic rats

Yazır

Polat

Utkan

et al. 2018

Psychiatry and Clinical Psychopharmacology

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OBJECTIVES: The impairment of cognitive functions in diabetes mellitus (DM) is well known. Nitric oxide (NO)-guanyly cyclase (GC)-cyclic guanosine monophosphate (cGMP) pathway is an important role in cognitive functions, and, consequently, phosphodiesterase-5 (PDE-5) inhibitors as well as NO-GC activators are of considerable interest in the treatment of cognitive deficits. Therefore, we aimed to investigate the effects of YC-1 (3-5-hydroxymethyl-2-furyl)-1-benzyl-indazole), an NO-GC activator, and zaprinast, a PDE-5 inhibitor, on cognitive dysfunction in streptozotocin (STZ)-induced diabetic rats. METHODS: Male Wistar rats were divided into five groups (nine rats in each): Control, Vehicle (DMSO), Diabetic (50 mg/kg/i.p. streptozotocin), Diabetic-YC-1 (1 mg/kg/day/i.p., for 4 weeks), and Diabetic-Zaprinast (10 mg/kg/day/i.p., for 4 weeks) group. The Morris water maze, passive avoidance, locomotor activity, and foot shock sensitivity tests were applied to assess the effect of YC-1 and zaprinast on learning and memory. To explore the mechanisms of YC-1 and zaprinast on learning and memory performance, protein expressions of brain-derived neurotrophic factor (BDNF) in hippocampus were examined immunohistochemically. RESULTS: Thirty days after the induction of DM, rats exhibited severe learning and memory dysfunctions associated with decreased BDNF expression. Both chronic YC-1 and zaprinast treatment improved cognitive performance and hippocampal BDNF expression in diabetic rats. In the locomotor activity and foot shock sensitivity test, no significant differences were observed between the groups. Furthermore, hyperglycaemia did not affect cognition enhancement effects of YC-1 or zaprinast in diabetic rats. CONCLUSIONS: Our findings highlight the beneficial effects of nitric oxide-guanylyl cyclase activators and PDE-5 inhibitors to improve cognitive function in diabetes.

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Selective and nonselective neuronal NOS inhibitors impair cognitive function in the three panel runway and passive avoidance tasks in rats

Cited by 9 publications

References 24 publications

Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice.

Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity disorder-like behaviors in mice.

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

Role of the nitric oxide-soluble guanylyl cyclase pathway in cognitive deficits in streptozotocin-induced diabetic rats

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