Prepulse Inhibition Deficits In Schizophrenia Research Articles

Dorsal striatum D1-expressing neurons are involved with sensorimotor gating on prepulse inhibition test.

Prepulse inhibition (PPI) is a behavioral test in which the startle reflex response to a high-intensity stimulus (pulse) is inhibited by the prior presentation of a weak stimulus (prepulse). The classic neural circuitry that mediates startle response is localized in the brainstem; however, recent studies point to the contribution of structures involved in higher cognitive functions in regulating the sensorimotor gating, particularly forebrain regions innervated by dopaminergic nuclei. The aim of the present study was to verify the role of dorsal striatum (DS) and dopaminergic transmitting mediated by D1 and D2 receptors on PPI test in rats. DS inactivation induced by muscimol injection did not affect PPI (%PPI and startle response), although it impaired the locomotor activity and caused catalepsy. Infusion of D1-like antagonist SCH23390 impaired %PPI but did not disturb the startle response and locomotor activity evaluated immediately after PPI test. D2 antagonist microinjection (sulpiride) did not affect %PPI and startle response, but impaired motor activity. These results point to an important role of DS, probably mediated by direct basal ganglia pathway, on modulation of sensorimotor gating, in accordance with clinical studies showing PPI deficits in schizophrenia, Tourette syndrome, and compulsive disorders - pathologies related to basal ganglia dysfunctions.

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia. We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes. We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls. We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions. The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.

Sleep, hypothalamus, and stigma

Dear colleagues, The current issue of the European Archives of Psychiatry and Clinical Neurosciences covers some topics not being at the center of current psychiatric research but nevertheless stimulating and potentially interesting to the field. In a representative German sample of 2,019 persons drawn from households, Schredl [1] investigated nightmare frequency and frequency of various nightmare topics. The five most common themes were falling, being chased, being paralyzed, being late, and the death of close persons. The author concludes that “even though several effects can be explained by the continuity hypothesis of dreaming, further research is needed to investigate the (possible metaphoric) relationship between nightmare topics and waking-life stressors”. Based on four well-described cases, Rossell et al. [2] develop a new cognitive model of delusions. All of these four cases had delusions as a consequence of post-traumatic brain injury without having a prior psychiatric illness. Overall, semantic processing was impaired in the four cases relative to a normative healthy control sample of 32 subjects. The cases performed better on tasks that required categorical identification, relative to the novel production of semantic information, which was poor in all four of the cases. These data are interpreted as preliminary evidence to support the notion of impaired semantic processing in persons with delusions. The dysfunction of the hypothalamic–pituitary–adrenal axis is connected to the pathophysiology of affective syndromes. In the well done selective overview, Pompili et al. [3] suggest that the overactivity of the HPA axis may well predict the onset of mood disorders and perhaps even suicidal behavior via abnormalities in the serotonergic system. A lot of attention is paid to the hypothalamus in affective disorders, while thalamic dysfunction and structural abnormalities are not a focus of research. In the study by Radenbach et al. [4], however, it was found that lithium treatment seems to have an impact on thalamic volumes in patients with bipolar disorder. Comparing patients with bipolar disorder and controls, no significant difference was found in this parameter, while subdividing the patient group into those treated with lithium compared to those without treatment revealed the above-mentioned difference. The study points to the importance of taking medication into account when researching biological parameters in major psychiatric disorders. Furthermore, it supports the notion of a neuroplastic effect of mood stabilizers and specifically lithium in psychiatric illnesses. The prepulse inhibition (PPI) of the startle reflex is often used as a biological parameter allowing to bridge the gap between psychiatric diseases and their animal models [5]. The paper by Molina et al. [6] explored whether there is a difference between the PPI and neuropsychological deficits in chronic schizophrenia. This study suggests that PPI deficits in schizophrenia may not be contributing to cognitive deficits typical to this illness, although it has to be taken into account that the patients revealed a non-significant PPI decrease. Finally, we want to draw attention to an interesting paper by Rusch et al. [7] exploring links between meritocratic worldviews and stigma. They measured just world believes for self and others as well as endorsement of the Protestant ethic in 85 people with schizophrenia, schizoaffective or affective disorder and in 50 members of the general public. Stigmatizing attitudes toward people with mental illness were assessed by self-report. The Protestant ethic may increase (self-)stigmatizing attitudes; just world believes for oneself, on the other hand, may lead to the unexpected implicit self-blame in stigmatized individuals. The authors conclude that public anti-stigma campaigns and initiatives to reduce self-stigma among people with mental illness should take worldviews into account. Furthermore, self-stigmatization might well be an overlooked finding however decreasing the willingness to seek psychiatric help [8].

The relationship between prepulse inhibition and general psychopathology in patients with schizophrenia treated with long-acting risperidone

Patients with schizophrenia exhibit impairments in prepulse inhibition (PPI) of the startle response. Available data suggest that atypical antipsychotics may be more effective than typical antipsychotics in improving PPI deficits in schizophrenia. However, previous studies have used between-subjects rather than longitudinal within-subjects designs to demonstrate superiority of particular atypical antipsychotics over typical antipsychotics in improving PPI in patients with schizophrenia. This longitudinal within-subjects test–retest study was designed to evaluate changes in PPI and clinical symptoms in patients with schizophrenia after switching from the conventional antipsychotic zuclopenthixol to long-acting injectable risperidone. PPI was measured in 45 chronic male patients with schizophrenia treated with zuclophentixol depot (session T1), and 12 weeks after switching to long-acting injectable risperidone (session T2). Thirty-six healthy control subjects were also evaluated. Patients with schizophrenia showed a significant improvement in PPI after changing to long-acting risperidone. Improvement of PPI deficits between T1 and T2 assessments correlated significantly with improvements in PANSS general psychopathology subscale scores. Our findings indicate that long-acting risperidone improves PPI deficits in subjects with chronic schizophrenia. These results also suggest that the PPI-restoring effect of risperidone may be related to improvement in symptoms other than positive and negative symptoms.

Prepulse inhibition deficits in schizophrenia are modified by smoking status

Background Schizophrenia is associated with high rates of cigarette smoking and deficits in sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle response. However, the relationship between PPI deficits and smoking status is unclear. We examined whether smoking status modifies PPI deficits in schizophrenia. Methods We studied PPI as a function of smoking status and schizophrenia diagnosis in four groups using a cross-sectional design: Smokers with schizophrenia (SS; n = 14), non-smokers with schizophrenia (SNS; n = 15), control smokers (CS; n = 11), and control non-smokers (CNS; n = 10). PPI in smokers was recorded under conditions of smoking satiation, and smoking status was verified biochemically. Results The Diagnosis × Smoking Status × Prepulse Interval interaction was significant ( F 11,140 = 5.01, p < 0.001). At all prepulse to pulse intervals (PPTPIs; 30, 60 and 120 ms), we found that SNS had reductions (~ 50%; p < 0.01) in PPI compared to CNS. However, when SS were compared to CS under conditions of smoking satiation, SS had comparable levels of PPI to CS, and significantly higher levels of PPI than SNS. Conclusions Our findings suggest that PPI deficits are present in nonsmokers with schizophrenia, and may be modified by smoking status. Acute smoking in schizophrenia is associated with an elevation of PPI to the levels in non-psychiatric control smokers. These findings have significant implications for understanding vulnerability to tobacco dependence in schizophrenia, which may lead to the development of more effective treatments for PPI deficits and tobacco dependence in this population.

Glycogen synthase kinase-3β heterozygote knockout mice as a model of findings in postmortem schizophrenia brain or as a model of behaviors mimicking lithium action: negative results

In mice glycogen synthase kinase (GSK)-3beta heterozygote knockout status was reported to cause reduced immobility in the Porsolt forced swim test and reduced amphetamine-induced hyperactivity, behaviors that mimic the effects of lithium. GSK-3beta protein and mRNA level and activity have been reported to be reduced in the postmortem brain of schizophrenia patients and this could suggest the involvement of GSK-3beta in the etiology of schizophrenia. However, apomorphine-induced stereotyping was reported to be unchanged in GSK-3beta heterozygote (HZ) knockout (KO) mice. As such behaviors are not always robust, study in another laboratory seemed indicated. Motor activity and coordination were assessed in the rotarod test. Behavior was studied in the following tests: pilocarpine-induced seizures model for lithium action, Porsolt forced swim test, tail suspension test, elevated plus-maze, large open field, startle response and prepulse inhibition of acoustic startle response, amphetamine-induced hyperactivity, and apomorphine-induced stereotypic climbing. We could not confirm the report that GSK-3beta HZ KO mice exhibit reduced immobility in the Porsolt forced swim or reduced amphetamine-induced hyperactivity in a manner mimicking the behavioral effects of lithium. We did not find increased apomorphine-induced stereotypic climbing or disruption of prepulse inhibition, suggesting that human postmortem findings regarding GSK-3beta in schizophrenia are not mediated by changes in dopamine receptors and are not the cause of prepulse inhibition deficits in schizophrenia. These data do not support the role of GSK-3beta in schizophrenia or in the mechanism of therapeutic action of lithium. Although differences in the genetic background of the GSK-3beta HZ KOs used in the present study compared with that of the previous study could be responsible, such results could suggest that the previously reported effects of GSK-3beta knockout on behavior are not robust.

Sensorimotor Gating of Schizophrenia Patients Is Influenced by 5-HT 2A Receptor Polymorphisms

Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), suggesting a sensorimotor gating deficit. The serotonin-2A receptor (5-HT(2A)R) has been implicated in both the pathogenesis of schizophrenia and the PPI deficits of schizophrenia patients. Moreover, both schizophrenia and PPI are thought to be inheritable. We investigated the impact of three 5-HT(2A)R polymorphisms (A-1438G, T102C, H452Y) on PPI in schizophrenia patients. We analyzed the 5-HT(2A)R A-1438G, T102C, and H452Y polymorphisms and assessed startle reactivity, habituation, and PPI of ASR in 68 Caucasian schizophrenia inpatients. Patients were also examined with the Positive and Negative Syndrome Scale. The 5-HT(2A)R A-1438G and T102C polymorphisms were in complete linkage disequilibrium. Patients carrying the T102C TT and the A-1438G AA allele show significantly higher PPI levels and a faster early habituation compared with all other variants. 5-HT(2A)R A-1438G and T102C genotype explained approximately 11% of the PPI and early habituation variance. In contrast, the 5-HT(2A)R H452Y polymorphism did not affect startle parameters. Our findings suggest that PPI and habituation are modulated by 5-HT(2A)R A-1438G and T102C genotype in schizophrenia. Consequently, alterations within brain 5-HT(2A)Rs may contribute to the PPI deficits in schizophrenia.

Strain differences in the disruption of prepulse inhibition of startle after systemic and intra-accumbens amphetamine administration

Background Sprague Dawley (SD) rats are significantly more sensitive than Long Evans (LE) rats to the disruption of prepulse inhibition (PPI) by systemically-administered dopamine (DA) agonists. This strain difference is heritable and insensitive to cross-fostering. Inherited differences in the ability of elevated DA activity to disrupt PPI may be useful for understanding the neural basis for PPI deficits in schizophrenia and other neuropsychiatric disorders. Methods PPI was tested in male SD and LE rats after amphetamine (AMPH) was administered: 1) subcutaneously (sc), or intra-cerebrally (ic) into 2) the nucleus accumbens core (NACc; medial or lateral subregions) or the NAC shell; 3) the anteromedial striatum (AMS) or 4) the posterior striatum (PS). Results SD and LE rats had comparable PPI levels after sc vehicle injection. PPI was disrupted in SD but not LE rats after sc AMPH injection. LE insensitivity to AMPH was confirmed after sc injection into non-pigmented dermis, demonstrating that it did not reflect melanocyte sequestration of AMPH. PPI was also disrupted in SD rats after ic infusion into the NACc (medial core: p < 0.005; lateral core: p < 0.001); in LE rats, these effects only approached threshold levels (medial core: p < 0.06; lateral core: p < 0.051). In SD rats, the highest dose of AMPH (40 μg) tended to reduce PPI after infusion into the AMS or PS, while in LE rats, this dose potentiated PPI after PS infusion. Comparisons of PPI in SD vs. LE rats revealed significant main effects of strain (SD > LE) after vehicle infusions into the NACc subregions and the PS. Comparisons of pre-infusion “matching” data, data from the first infusion day, and data from separate rats in a “mock-infusion” paradigm is consistent with the possibility that SD > LE PPI after ic vehicle infusion reflects the impact of restraint stress on PPI in LE rats. Conclusions PPI is disrupted by AMPH administered sc or into the NACc in SD but not LE rats. Reduced PPI after ic vehicle infusion in LE vs. SD rats may reflect greater PPI-reducing effects of restraint stress in LE rats. The differential impact of restraint on PPI in SD vs. LE rats complicates the interpretation of strain differences in the effects of ic manipulations, but may provide an avenue for investigating the basis for differences in vulnerability to the gating-disruptive effects of stress. Supported by MH68366, MH01436.

A preliminary study of the effects of cigarette smoking on prepulse inhibition in schizophrenia: Involvement of nicotinic receptor mechanisms

Background Schizophrenics exhibit deficits in prepulse inhibition (PPI) of the startle response, and have high rates of cigarette smoking. We evaluated the effects of cigarette smoking on PPI deficits in schizophrenia, and the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related PPI enhancement. Methods PPI was assessed at baseline, after overnight abstinence, and after smoking reinstatement during three separate test weeks in nicotine-dependent schizophrenia ( n = 15) and control ( n = 14) smokers pre-treated with the nAChR antagonist mecamylamine (MEC; 0.0, 5.0 or 10.0 mg/day). Results PPI was comparable between schizophrenia and control smokers after ad lib cigarette smoking. Overnight smoking abstinence significantly reduced PPI, while smoking reinstatement reversed abstinence-induced worsening of PPI deficits in schizophrenia. However, acute abstinence and reinstatement did not alter PPI in controls. PPI enhancement by smoking reinstatement in schizophrenia was dose-dependently blocked by MEC, whereas MEC had no effect on PPI in control smokers. Conclusions These results suggest that: 1) Non-deprived smokers with schizophrenia have comparable levels of PPI to non-deprived smoking controls; 2) In schizophrenia, PPI is impaired by smoking abstinence and improved by acute smoking reinstatement, and; 3) enhancement of PPI by cigarette smoking in schizophrenia is mediated by stimulation of central nAChRs. Our findings may contribute to understanding the increased vulnerability to nicotine dependence in schizophrenia, with implications for treatment of PPI deficits in this disorder.

Prepulse-elicited motor reactions do not differ between schizophrenia patients and control subjects.

Electromyographic (EMG) measures were made of the eyeblink response to stimuli 2-16 dB over a 70-dBA noise background as well as the eyeblink response to startling 115-dBA pulses in 15 schizophrenia patients and 10 control subjects. In patients and in control subjects, weak stimuli did not elicit EMG activation. Startling stimuli elicited robust EMG activation in both groups. Compared with control subjects, schizophrenia patients are not more sensitive to motor-activating effects of weak acoustic stimuli that served as prepulses in published reports of prepulse inhibition deficits in schizophrenia. Thus, differential sensitivity to the motor-activating effects of prepulses should not contribute to reduced prepulse inhibition in schizophrenia patients versus control subjects.

Sex differences in prepulse inhibition deficits in chronic schizophrenia

Recent years have seen a dramatic growth in the number of studies using prepulse inhibition (PPI) paradigms to index information processing deficits in schizophrenia. There are, however, robust sex differences in PPI in healthy subjects, with women exhibiting less PPI than men in the absence of any psychopathology. To investigate the role of sex in prepulse modification deficits in the long-term course of schizophrenia, we assessed PPI (response inhibition with the prepulse preceding the pulse by 30–150 ms) and prepulse facilitation (PPF; response facilitation with the prepulse preceding the pulse by 1000 ms) of the acoustic startle response in 42 chronic schizophrenia patients (27 men; all 42 on typical antipsychotics) and 35 controls (15 men). The results revealed that healthy women showed less PPI than healthy men. Men with schizophrenia showed less PPI compared to healthy men, but women with schizophrenia did not differ in PPI from healthy women. Age of illness onset negatively correlated to PPI in male patients. There was no significant effect of sex in PPF, and although patients (regardless of sex) showed less PPF relative to controls, this effect was abolished when the current age was co-varied for. These findings indicate sex differences in PPI deficits in schizophrenia. Future studies of schizophrenia patients need to take sex and age of subjects into account to optimise the investigation of PPI deficits, and their clinical, neural, and pharmacological correlates.

Effects of typical and atypical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research.

Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). PPI provides a simple operational measure of sensorimotor gating, serving to prevent the interruption of ongoing perceptual and early sensory analysis. In accord with postulated deficits in early stages of information processing, there is ample evidence that PPI is disrupted in individuals with schizophrenia. PPI in animals is thought to represent a well-validated model for evaluating potential new treatments for schizophrenia. Currently, available data on the differential effects of typical and atypical antipsychotics suggest that atypical antipsychotics, in particular clozapine and risperidone, may be more effective than typical antipsychotics in improving PPI deficits in schizophrenia. However, studies have so far used small samples and/or between-subjects designs, and not examined the effects of other concomitant medications that may also influence PPI. The directions are identified for further applications of this model using within-subjects longitudinal designs and reasonable sample sizes to establish superiority of particular atypical antipsychotics over typical antipsychotics in improving PPI in schizophrenic populations.

Vasopressin-deficient rats exhibit sensorimotor gating deficits that are reversed by subchronic haloperidol

Background: Brattleboro (BB) rats are Long Evans rats with a single base pair genetic mutation that impairs their ability to synthesize vasopressin, a neurotransmitter and neurohormone. Brattleboro rats are known to have deficits in memory, emotional reactivity, motivation, attention, and social recognition, abnormalities associated with schizophrenia. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is a measure of sensorimotor gating. Prepulse inhibition is deficient in unmedicated schizophrenia patients, and PPI deficits in schizophrenia may be related to the cognitive and behavioral abnormalities associated with this disorder. In this study we tested the hypothesis that BB rats exhibit PPI deficits analogous to those exhibited by schizophrenia patients. Methods: In one experiment, BB rats homozygous (BB-Ho) or heterozygous (BB-Hz) for the mutated vasopressin gene were compared with normal Long Evans (LE) rats from the same breeder source. In separate studies, BB-Ho and LE rats were treated with acute or subchronic (22 days) injections of haloperidol. Results: Both BB-Ho and BB-Hz rats had significantly higher ASR and significantly lower PPI compared with LE rats, with BB-Ho rats exhibiting the lowest PPI among all three genotypes. Furthermore, a single subcutaneous (SC) injection of haloperidol (0.5 mg/kg) did not reverse the PPI deficits in BB rats. In contrast, daily SC administration of haloperidol for 22 days reversed PPI deficits in BB rats. Conclusions: These results suggest that PPI deficient BB rats may be an important genetic model of PPI deficits, which may help elucidate genetic, pharmacologic, and pathophysiologic mechanisms underlying PPI deficits and the effects of antipsychotic drugs on PPI.

The effect of neuroleptic medication on prepulse inhibition in schizophrenia patients: current status and future issues.

Prepulse inhibition (PPI) of the startle reflex is a powerful tool for investigating sensorimotor gating in both animals and humans. Evidence of impaired PPI in patients with schizophrenia suggests that PPI performance might serve as a promising model to investigate the neurobiological mechanisms of this disorder. Animal data show that experimentally induced PPI deficits can be removed by the administration of antipsychotic agents. Recent clinical studies suggest that neuroleptic medication is capable of improving deficient PPI performance in schizophrenia patients as well. The present paper reviews the published data on PPI performance in schizophrenia patients, focussing on medication effects. Using a modified meta-analytic approach, the consistency of PPI deficits in schizophrenia patients across studies is explored. In particular, methodological issues of defining PPI deficits and assessing PPI improvements are considered. Literature search produced 12 original studies that investigated PPI performance in schizophrenia patients using comparable experimental conditions. Percentage change scores were calculated to compare the actual amount of PPI observed in schizophrenia patients and healthy controls across studies. Results revealed that the amount of PPI in medicated schizophrenia patients was fairly consistent across all studies. For medicated schizophrenia patients, the amount of PPI varied between 30% and 65% for the critical lead intervals. Moreover, medicated patients showed around 20% less PPI than healthy controls. Whether these group differences were statistically significant depended on the composition of the control group that showed large variability across studies. To delineate the effects of neuroleptic medication on PPI performance more precisely, future research should not further rely on between-group comparisons. Rather, future clinical research should take advantage of longitudinal designs to disentangle state-dependent medication effects from more stable, trait-linked factors that contribute to PPI deficits in schizophrenia.

Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication.

Prepulse inhibition of the startle reflex response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect represents an operational index of sensorimotor gating and is found to be deficient in schizophrenia. Prepulse inhibition deficits in schizophrenia seem to be partially normalized by typical antipsychotics and more fully by some atypical antipsychotics. Early onset of schizophrenia, particularly in men, has been associated with abnormal brain maturation, profound neuropsychological deficits, and less responsiveness to antipsychotic medication. We evaluated the effects of the age of onset of illness, current positive and negative symptoms, and the type of medication (typical vs atypical) on prepulse inhibition of the startle response in schizophrenia. Thirty-eight male schizophrenic patients and 20 healthy male controls underwent testing for prepulse inhibition of the acoustic startle response. Earlier onset of illness was associated with reduced prepulse inhibition, while adult onset of illness was not. No significant relationships occurred between current symptoms and prepulse inhibition. Patients given typical, but not atypical, antipsychotics exhibited less prepulse inhibition compared with healthy controls. Early onset of illness is associated with profound deficits in prepulse inhibition of the startle response in men with schizophrenia.

The Effects of M100907 in Pharmacological and Developmental Animal Models of Prepulse Inhibition Deficits in Schizophrenia

Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of the startle response. M100907, a selective 5-HT2A-receptor antagonist that has been developed for clinical testing as an antipsychotic in schizophrenic patients, has been tested in several animal models of the gating deficits in schizophrenia, including PPI. Previous studies have shown that M100907 blocks or reduces the disruptive effects of hallucinogenic 5-HT2 agonists (e.g., DOI) and psychotomimetic NMDA antagonists (e.g., phencyclidine) on PPI. In the present paper, we report the results of three studies conducted to determine the effects of M100907 on apomorphine-induced disruption (one experiment) and isolation rearing-induced disruption of PPI in rats (two experiments). Results showed that M100907 failed to reduce the disruption of PPI caused by the dopamine agonist apomorphine. Nevertheless, M100907 partially reduced the disruption of PPI caused by isolation rearing. Thus, M100907 shows efficacy as a putative antipsychotic in nondopaminergic PPI models of the sensorimotor gating deficits in schizophrenia. [