Roles of 5-HT2 receptors in effects of DOM,ketamine and methamphetamine on prepulse inhibition in Sprague Dawley rats

OBJECTIVE Prepulse inhibition(PPI)of the acoustic startle response provides a measure of sensorimotor gating system mecha⁃nisms,which is known to be impaired in schizo⁃phrenia patients.We assessed the effects of the 5-HT2A/2C receptor agonist(±)2,5-dimethoxy-4-methylamphetamine(DOM),the NMDA receptor antagonist ketamine,the dopamine receptor ago⁃nist methamphetamine(Meth)on PPI and the startle magnitude in SD rats.METHODS AND RESULTS Systemic administration of the three compounds all dose-dependently reduced PPI.However,as far as startle magnitude,only DOM at the doses of 3 mg·kg-1 reduced that,while both ketamine and Meth did not change the startle magnitudes.Furthermore,to determine whether 5-HT2A receptor mediate this effect,the non-spe⁃cific 5-HT2 receptor antagonist cyproheptadine,specific 5-HT2A receptor antagonist ketanserin and specific 5-HT2C receptor antagonist SB242084 were tested.Cyproheptadine,ketan⁃serin and SB242084 did not alter startle ampli⁃tude by themselves in SD rats and only ketanserin slightly increased PPI at higher dose(3 mg·kg-1).PPI impairment induced by DOM was restored by pretreatment of cyproheptadine(1 mg·kg-1)and ketanserin(1 mg·kg-1),while not by pretreat⁃ment of SB242084(1 mg·kg-1).Damage of PPI induced by ketamine and Meth was not reversed by cyproheptadine(1 and 5 mg·kg-1).CONCLU⁃SION The receptor mechanisms underlying the disruption of PPI caused by DOM,ketamine and Meth were different from each other,at least 5-HT2A receptor was not the junction receptor for which the three chemicals acted.

No Correlation between <i>AVPR</i>1A Promoter Polymorphisms and Prepulse Inhibition in Patients with Nocturnal Enuresis

Introduction: A correlation between AVPR1A promoter polymorphisms and prepulse inhibition (PPI) of startle reflexes has been described in healthy adults. Many children with nocturnal enuresis (NE) have a reduced PPI and treatment with desamino arginine vasopressin (dDAVP), a ligand of the arginine vasopressin receptor 1A (AVPR1A), and both improve clanical symptoms and significantly increase PPI. Methods: In 17 children (median 9.1 years, range 6.4-17.3) with NE, promoter repeats within the RS1 and RS3 regions of AVPR1A were quantified and correlated to PPI (native and age-adjusted). Results: No direct correlation was found between the number of promoter repeats at RS1 and PPI (correlation coefficient—0.240, p = 0.346) or RS3 and PPI (correlation coefficient—0.0192, p = 0.936), with no change through age-adjustment of PPI. The different RS3 length subgroups did not show differences in PPI, nor did differentiation of NE according to clinical subtype or treatment response to dDAVP show differences in the number of promoter repeats. Conclusion: The missing reproducibility of the correlation between AVPR1A promoter polymorphisms and PPI in a group with wide range of PPI suggests a more complex interaction. Therefore, further investigations are needed to analyze this very plausible interaction. Conditions with a reduced PPI, such as enuresis, schizophrenia or autism, are particularly interesting for this research.

Prepulse inhibition deficits in antipsychotic-na-ve first-episode schizophrenia:a meta-analysis

Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.

Chronic morphine treatment decreases acoustic startle response and prepulse inhibition in rats

The reward-related effects of addictive drugs primarily act via the dopamine system, which also plays an important role in sensorimotor gating. The mesolimbic dopamine system is the common pathway of drug addiction and sensorimotor gating. However, the way in which addictive drugs affect sensorimotor gating is currently unclear. In previous studies, we examined the effects of morphine treatment on sensory gating in the hippocampus. The present study investigated the effects of morphine on sensorimotor gating in rats during chronic morphine treatment and withdrawal. Rats were examined during treatment with morphine for 10 successive days, followed by a withdrawal period. Acoustic startle responses to a single startle stimulus (115 dB SPL) and prepulse inhibition responses were recorded. The results showed that acoustic startle responses were attenuated during morphine treatment, but not during withdrawal. PPI was impaired in the last 2 morphine treatment days, but returned to a normal level during withdrawal.

Prepulse Inhibition of Auditory Cortical Responses in the Caudolateral Superior Temporal Gyrus in Macaca mulatta

Prepulse inhibition(PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the PPI of cortical responses. We recorded local field potentials(LFPs) in four monkeys and investigated whether the PPI of auditory cortical responses(alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyrus(STGcb). We also investigated whether the presence of a conspecific, which draws attention away from the auditory stimuli, affects the PPI of auditory cortical responses. The PPI paradigm consisted of Pulse-only and Prepulse + Pulse trials that were presented randomly while the monkey was alone(ALONE) and while another monkey was present in the same room(ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related inhibition of the N1 amplitude of the evoked responses and cortical oscillations to the Pulse were not affected by the presence of a conspecific. In contrast, gamma oscillations and the amplitude of the N1 response to Pulse-only were suppressed in the ACCOMP condition compared to the ALONE condition. Thesefindings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is a pre-attentive inhibitory process that is independent of attentional modulation.

Optimization of 4.7-keV X-ray titanium sources driven by 100-ps laser pulses

An experiment with thin titanium foils irradiated by two pulses delayed in time is conducted on the Shenguang-II laser facility.A prepulse induces an underdense plasma,2-ns later a main pulse(λ L = 0.35 μm,E L ≈ 120 J,τ L ≈ 100 ps) is injected into the underdense plasma and produces strong line emission from the titanium K shell(i.e.,He α at 4.7 keV).Data show that the intensity of 4.7-keV X-ray emission with the prepulse is approximately twice more than without the prepulse,and can be used as a backlighting source satisfying the diagnostic requirements for dense plasma probing.Highquality plasma images are obtained with the backlighting 4.7-keV X-rays in a Rayleigh-Taylor hydrodynamic instability experiment.

Acoustic startle reflex and pre-pulse inhibition in tinnitus patients

Gap induced pie-pulse inhibition(Gap-PPI) of acoustic startle reflex has been used as a measurement of tinnitus in animal models.However,whether this test is sensitive to detect tinnitus in humans is still unclear.Based on the testing procedure used in animal studies,a human subject testing method was formulated and conducted to investigate if a similar result could be found in tinnitus patients.Audiologic and tinnitus assessments and acoustic startle reflex measurements were performed on seven tinnitus subjects and nine age matched subjects without tinnitus.There was no significant difference found between the control and tinnitus group on the Gap-PPl across the frequencies evaluated.The amplitude of the startle response in the tinnitus group with normal hearing thresholds was significantly higher than the control group and those with tinnitus and hearing loss.This preliminary result suggests that hyperexcitability in the central auditory system may be involved in tinnitus.There was no correlation between hearing thresholds and the increased amplitude of startle response.

Aberrant Light-Induced Depression is Associated with Impaired Sensorimotor Gating in Mice

Mice subjected to an irregular light-dark cycle are known to lose their capacity to synchronize their behavioral rhythm to environmental light, and to show endophenotypes related to depressive disorders. Here we observed that a susceptible strain of mice (C3H/HeJ) subjected to an irregular 3.5 hr:3.5 hr light-dark cycle showed an enhanced acoustic startle reflex and deficits in prepulse inhibition. As impaired sensorimotor gating is associated with the onset of a variety of mental disorders such as schizophrenia and major depressive disorder, irregular environmental light without circadian photo-entrainment may cause stress that has the potential to be involved in humans’ susceptibility to neuropsychiatric abnormalities.

Genetic Rat Models of Schizophrenia-Relevant Symptoms

It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.

Experimental investigation of Ne-like Ti X-ray laser

The experiment on Ne-like X-ray laser has been carried out successfully at the Xingguang Laser Facility by means of a transmission-reflection line focus system and a prepulse 5 ns before the main pulse. The TiXIII losing on 3s-3p J=0- 1 transition has been observed and the gain coefficient measured. The, dependence of the intensities, the divergences and defection angles of losing line on driving energies and prepulses are investigated.

A Study on the Effect of Risperidone on PPI and P50 Deficit in FirstEpisode and Chronic Patients with Schizophrenia

Objective To investigate the effect of atypical antipsychotics risperidone on prepulse inhibition of the startle reflex(PPI) and P50 deficit in first-episode and chronic patients with schizophrenia. Methods PPI and P50 were tested and compared in 81 first-episode acute schizophrenia patients and 92 chronic schizophrenia patients before and after the risperidone. Results There was no significant difference in PPI and P50 indices between the two groups before treatment(P>0. 05); 2) there was no significant correlation between PPI & P50 inhibition indices and PANSS score, onset frequency and disease course(P>0.05); 3) Except the significant group main effect for S2 amplitude in P50(P=0. 02), there was no significant change for main effect and interaction of the other P50 and PPI inhibition ratio indices after treatment(P>0. 05). The effect of risperidone on PPI and P50 measurement index had nothing to do with the curative effect. Conclusion There exists a deficit in sensory gating inhibition in both first-episode schizophrenia and chronic schizophrenia, which is relatively independent from disease course. The risperidone is not effective in improving PPI and P50 inhibition deficit.