Clerodendrum inermeLeaf Extract Alleviates Animal Behaviors, Hyperlocomotion, and Prepulse Inhibition Disruptions, Mimicking Tourette Syndrome and Schizophrenia

Previously, we found a patient with intractable motor tic disorder, a spectrum of Tourette syndrome (TS), responsive to the ground leaf juice ofClerodendrum inerme(CI). Here, we examined the effect of the ethanol extract ofCIleaves (CIextract) on animal behaviors mimicking TS, hyperlocomotion, and sensorimotor gating deficit. The latter is also observed in schizophrenic patients and can be reflected by a disruption of prepulse inhibition of acoustic startle response (PPI) in animal models induced by methamphetamine and NMDA channel blockers (ketamine or MK-801), based on hyperdopaminergic and hypoglutamatergic hypotheses, respectively.CIextract (10–300 mg/kg,i.p.) dose-dependently inhibited hyperlocomotion induced by methamphetamine (2 mg/kg,i.p.) and PPI disruptions induced by methamphetamine, ketamine (30 mg/kg,i.p.), and MK-801 (0.3 mg/kg,i.p.) but did not affect spontaneous locomotor activity, rotarod performance, and grip force. These results suggest thatCIextract can relieve hyperlocomotion and improve sensorimotor gating deficit, supporting the therapeutic potential ofCIfor TS and schizophrenia.

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Sensorimotor Gating in Depressed and Euthymic Patients with Bipolar Disorder: Analysis on Prepulse Inhibition of Acoustic Startle Response Stratified by Gender and State

Frontiers in Psychiatry ◽

10.3389/fpsyt.2018.00123 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 7

Author(s):

Junko Matsuo ◽

Miho Ota ◽

Shinsuke Hidese ◽

Toshiya Teraishi ◽

Hiroaki Hori ◽

...

Keyword(s):

Bipolar Disorder ◽

Prepulse Inhibition ◽

Startle Response ◽

Acoustic Startle ◽

Acoustic Startle Response ◽

Sensorimotor Gating

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Nitric oxide modulates dopaminergic regulation of prepulse inhibition in the basolateral amygdala

Journal of Psychopharmacology ◽

10.1177/0269881110379282 ◽

2010 ◽

Vol 25 (12) ◽

pp. 1639-1648 ◽

Cited By ~ 8

Author(s):

C Salum ◽

AC Issy ◽

ML Brandão ◽

FS Guimarães ◽

EA Del Bel

Keyword(s):

Nitric Oxide ◽

Prepulse Inhibition ◽

Basolateral Amygdala ◽

Acoustic Startle ◽

Acoustic Startle Response ◽

Sensorimotor Gating ◽

Disruptive Effect ◽

Sound Pulse ◽

Systemic Injection ◽

Local Inhibition

Systemic injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (LNO) prevents the disruptive effect of amphetamine (Amph) on prepulse inhibition (PPI), a sensorimotor gating model in which the amplitude of the acoustic startle response (ASR) to a startling sound (pulse) is reduced when preceded immediately by a weaker stimulus (prepulse). Given that dopamine (DA) projections to the basolateral amygdala (BLA) are involved in the control of information processing, our aim was to investigate if intra-BLA administration of LNO would modify the disruption caused by the DA agonists, Amph, apomorphine (Apo) and quinpirole (QNP), on PPI. Male Wistar rats received bilateral intra-BLA microinjections (0.2 µL/min/side) of combined treatments (saline or LNO 11 µg followed by saline, QNP 3 µg, Apo 10 µg or Amph 30 µg). PPI was disrupted by intra-BLA Apo, QNP or Amph but not by LNO. Prior bilateral intra-BLA injection of LNO prevented the Apo- and QNP-induced disruption of PPI but did not affect that caused by Amph. APO- or QNP-induced increases in ASR to prepulse + pulse were also restored by LNO. Since local inhibition of NO formation affected the effects of direct, but not indirect, DA agonists, the results suggest that this modulation is not occurring at the level of DA release but may involve complex interactions with other neurotransmitter systems.

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Histamine H3 receptor activation reduces the impairment in prepulse inhibition (PPI) of the acoustic startle response and Akt phosphorylation induced by MK-801 (dizocilpine), antagonist at N-Methyl-d-Aspartate (NMDA) receptors

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2019.109653 ◽

2019 ◽

Vol 94 ◽

pp. 109653 ◽

Cited By ~ 1

Author(s):

Guillermo Aquino-Miranda ◽

Nayeli Rivera-Ramírez ◽

Ricardo Márquez-Gómez ◽

Juan Escamilla-Sánchez ◽

Raúl González-Pantoja ◽

...

Keyword(s):

Nmda Receptors ◽

Prepulse Inhibition ◽

Startle Response ◽

Acoustic Startle ◽

Acoustic Startle Response ◽

Receptor Activation ◽

Histamine H3 Receptor ◽

Mk 801 ◽

Akt Phosphorylation ◽

Histamine H3

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Genetic Determinants of Gating Functions: Do We Get Closer to Understanding Schizophrenia Etiopathogenesis?

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.550225 ◽

2020 ◽

Vol 11 ◽

Author(s):

Rastislav Rovný ◽

Dominika Besterciová ◽

Igor Riečanský

Keyword(s):

Prepulse Inhibition ◽

Association Studies ◽

Acoustic Startle ◽

Acoustic Startle Response ◽

Genetic Association Studies ◽

Sensorimotor Gating ◽

Sensory Gating ◽

Eligibility Criteria ◽

Level Of Evidence ◽

Sensory Stimuli

Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the pathogenesis of several neuropsychiatric disorders, in particular schizophrenia. Gating is disrupted both in schizophrenia patients and their unaffected relatives, suggesting that gating deficit may represent a biomarker associated with a genetic liability to the disorder. To assess the strength of the evidence for the etiopathogenetic links between genetic variation, gating efficiency, and schizophrenia, we carried out a systematic review of human genetic association studies of sensory gating (suppression of the P50 component of the auditory event-related brain potential) and sensorimotor gating (prepulse inhibition of the acoustic startle response). Sixty-three full-text articles met the eligibility criteria for inclusion in the review. In total, 117 genetic variants were reported to be associated with gating functions: 33 variants for sensory gating, 80 variants for sensorimotor gating, and four variants for both sensory and sensorimotor gating. However, only five of these associations (four for prepulse inhibition—CHRNA3 rs1317286, COMT rs4680, HTR2A rs6311, and TCF4 rs9960767, and one for P50 suppression—CHRNA7 rs67158670) were consistently replicated in independent samples. Although these variants and genes were all implicated in schizophrenia in research studies, only two polymorphisms (HTR2A rs6311 and TCF4 rs9960767) were also reported to be associated with schizophrenia at a meta-analytic or genome-wide level of evidence. Thus, although gating is widely considered as an important endophenotype of schizophrenia, these findings demonstrate that evidence for a common genetic etiology of impaired gating functions and schizophrenia is yet unsatisfactory, warranting further studies in this field.

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