ROCK inhibition produces anxiety-related behaviors in mice

Saitoh, Akiyoshi; Yamada, Mitsuhiko; Kobayashi, Shinya; Hirose, Noritaka; Honda, Kazuo; Kamei, Junzo

doi:10.1007/s00213-006-0466-4

Cited by 34 publications

(22 citation statements)

References 58 publications

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“…Sham-operated mice showed similar head-dipping behavior. Previously, it has been reported that decreased head-dipping behavior might reflect an anxiety-like behavior in mice (17,20,37). Furthermore, social isolation has been proposed as a model for anxiety, since socially isolated animals are known to exhibit anxiety-like behavior in the elevated plus maze and the open field (34,35).…”

Section: Discussionmentioning

confidence: 99%

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Changes in Emotional Behavior of Mice in the Hole-Board Test After Olfactory Bulbectomy

et al. 2006

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Abstract. The most consistent behavioral change caused by olfactory bulbectomy (OBX) is a hyperemotional response to novel environmental stimuli. The aim of this study was to characterize the emotional behavior of OBX mice using the hole-board test. After the olfactory bulbs were lesioned, sham and OBX mice were housed in single cages for 14 days. The number of head-dips in the hole-board test in single-housed OBX mice was significantly greater than that in single-housed sham mice. The head-dipping behaviors in single-housed sham and OBX mice were reversed by treatment with diazepam, a typical benzodiazepine anxiolytic. (±)-8-Hydroxy-2-(di-n-propylamino) tetraline hydrobromide (8-OH-DPAT), a selective 5-HT 1A -receptor agonist that has a non-benzodiazepine anxiolytic-like effect, and (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl benzamide (SNC80), a δ-opioid-receptor agonist, also significantly reversed the number of head-dips in single-housed sham and OBX mice. In conclusion, we suggest that the single-housed OBX mice showed heightened emotional behavior (e.g., increase in head-dipping behavior) in the hole-board test. In addition, we suggest that the hyperemotional behavior characterized by head-dipping behavior in OBX mice was selectively reversed by benzodiazepine and non-benzodiazepine anxiolytics.

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Section: Discussionmentioning

confidence: 99%

“…The results in the hole-board test were determined automatically as described previously (37). The holeboard apparatus was made of a gray wooden box (50 × 50 × 50 cm) with four holes 3 cm in diameter equally spaced in the floor and placed in indirect light (40 lx).…”

Section: Hole-board Testmentioning

confidence: 99%

Changes in Emotional Behavior of Mice in the Hole-Board Test After Olfactory Bulbectomy

et al. 2006

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“…It is evident that the actin cytoskeleton is involved in synaptic plasticity and neuronal morphogenesis underlying the formation of fear memory. For example, a disruption in the actin cytoskeleton assembly in the adult brain impairs both cued and contextual fear conditioning (8)(9)(10), and several actin-regulatory proteins have been shown to be involved in synaptic plasticity and neuronal morphogenesis associated with memory formation (11)(12)(13)(14)(15).…”

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confidence: 99%

MicroRNA-mediated disruption of dendritogenesis during a critical period of development influences cognitive capacity later in life

Lin

Ponnusamy

Widagdo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The prenatal period of cortical development is important for the establishment of neural circuitry and functional connectivity of the brain; however, the molecular mechanisms underlying this process remain unclear. Here we report that disruption of the actin-cytoskeletal network in the developing mouse prefrontal cortex alters dendritic morphogenesis and synapse formation, leading to enhanced formation of fear-related memory in adulthood. These effects are mediated by a brain-enriched microRNA, miR-9, through its negative regulation of diaphanous homologous protein 1 (Diap1), a key organizer of the actin cytoskeletal assembly. Our findings not only revealed important regulation of dendritogenesis and synaptogenesis during early brain development but also demonstrated a tight link between these early developmental events and cognitive functions later in life.miR-9 | learning | memory | Diap1 | dendritogenesis P erturbation during the critical period of perinatal cortical development influences the functional connectivity of the brain and can lead to an increased propensity toward neurological disorders such as anxiety, schizophrenia, and autism spectrum disorders (1-3). Neuronal maturation involves distinct, highly regulated events, including neuronal differentiation and migration, dendritogenesis, axon formation/guidance, and synaptogenesis, among others. However, precisely how these events are regulated and how they orchestrate brain development and cognitive function remain largely unknown.Fear-related learning and memory play a significant role in the development of anxiety disorders. Cortical dysfunction is associated with emotional disturbances, which are underpinned by impaired fear extinction, and an inefficient termination of physiological stress responses (4, 5). The medial prefrontal cortex (mPFC) is a primary mediator of fear-related learning and memory (6, 7). It is evident that the actin cytoskeleton is involved in synaptic plasticity and neuronal morphogenesis underlying the formation of fear memory. For example, a disruption in the actin cytoskeleton assembly in the adult brain impairs both cued and contextual fear conditioning (8-10), and several actin-regulatory proteins have been shown to be involved in synaptic plasticity and neuronal morphogenesis associated with memory formation (11-15).Small noncoding RNAs, and miRNAs in particular, have emerged as a major regulatory mechanism that precisely controls the level of gene expression. In invertebrates, miRNAs play essential roles in regulating developmental timing. For example, in Caenorhabditis elegans the succession of certain cell fates from first to second larval stage relies on the induction of miRNA lin-4 expression at the first larval stage and reduction of lin-14 activity via base-pairing interactions with its 3′ UTR (16,17). In mice, miRNAs have been shown to be involved in rapidly fine-tuning the expression of their target mRNAs and in regulating cognitive function (18,19). In our study, we found that the expression of the actin polyme...

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“…However, Y-27632 failed to change spontaneous alteration performance in the Y-maze test. Taken together, these results indicated that ROCK inhibition may increase anxiety-related behaviors (Saitoh et al, 2006). Moreover, intratrigeminal ganglionic injection of lysophosphatidic acid induced neuropathic pain-like behavior and demyelination in rats were reduced by Y-27632 (10 nmol/3 μl) pretreatment into the same ganglion (Ahn et al, 2009).…”

Section: Discussionmentioning

confidence: 88%

Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats

İnan

Soner

Şahin

2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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ROCK inhibition produces anxiety-related behaviors in mice

Cited by 34 publications

References 58 publications

Changes in Emotional Behavior of Mice in the Hole-Board Test After Olfactory Bulbectomy

Changes in Emotional Behavior of Mice in the Hole-Board Test After Olfactory Bulbectomy

MicroRNA-mediated disruption of dendritogenesis during a critical period of development influences cognitive capacity later in life

Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats

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