Prepulse inhibition

About: Prepulse inhibition is a research topic. Over the lifetime, 2336 publications have been published within this topic receiving 112644 citations. The topic is also known as: GO:0060134 & pre-pulse inhibition.

Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

Abstract: Rationale: Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30–500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). Objective: This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. Methods: All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. Results: The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps post-traumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. Conclusions: Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.

Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.

Abstract: Rationale: Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. Similar deficits in PPI are produced in rats by pharmacological or developmental manipulations. These experimentally induced PPI deficits in rats are clearly not animal models of schizophrenia per se, but appear to provide models of sensorimotor gating deficits in schizophrenia patients that have face, predictive, and construct validity. In rodents, disruptions in PPI of startle are produced by: stimulation of D2 dopamine (DA) receptors, produced by amphetamine or apomorphine; activation of serotonergic systems, produced by serotonin (5-HT) releasers or direct agonists at multiple serotonin receptors; and blockade of N-methyl-D-aspartate (NMDA) receptors, produced by drugs such as phencyclidine (PCP). Accordingly, dopaminergic, serotonergic, and glutamatergic models of disrupted PPI have evolved and have been applied to the identification of potential antipsychotic treatments. In addition, some developmental manipulations, such as isolation rearing, have provided non-pharmacological animal models of the PPI deficits seen in schizophrenia. Objective: This review summarizes and evaluates studies assessing the effects of systemic drug administrations on PPI in rats. Methods: Studies examining systemic drug effects on PPI in rats prior to January 15, 2001 were compiled and organized into six annotated appendices. Based on this catalog of studies, the specific advantages and disadvantages of each of the four main PPI models used in the study of antipsychotic drugs were critically evaluated. Results: Despite some notable inconsistencies, the literature provides strong support for significant disruptions in PPI in rats produced by DA agonists, 5-HT2 agonists, NMDA antagonists, and isolation rearing. Each of these models exhibits sensitivity to at least some antipsychotic medications. While the PPI model based on the effects of direct DA agonists is the most well-validated for the identification of known antipsychotics, the isolation rearing model also appears to be sensitive to both typical and atypical antipsychotics. The 5-HT PPI model is less generally sensitive to antipsychotic medications, but can provide insight into the contribution of serotonergic systems to the actions of newer antipsychotics that act upon multiple receptors. The deficits in PPI produced by NMDA antagonists appear to be more sensitive to clozapine-like atypical antipsychotics than to typical antipsychotics. Hence, despite some exceptions to this generalization, the NMDA PPI model might aid in the identification of novel or atypical antipsychotic medications. Conclusions: Studies of drug effects on PPI in rats have generated four distinctive models that have utility in the identification of antipsychotic medications. Because each of these models has specific advantages and disadvantages, the choice of model to be used depends upon the question being addressed. This review should help to guide such decisions.

Sensorimotor Gating and Schizophrenia: Human and Animal Model Studies

Abstract: • Human and animal model studies of sensorimotor gating allow us to understand the functional significance of attentional abnormalities and monoaminergic alterations in patients with schizophrenic disorders. Clinically, schizophrenic patients report oversensitivity to sensory stimulation that theoretically correlates with stimulus overload and leads to cognitive fragmentation. Paradigms using cortical event-related potentials and the prepulse inhibition of startle responses show that schizophrenic patients also have impaired central nervous system inhibition (sensorimotor gating). Animal model studies demonstrate that increased systemic aminergic activity and increased nucleus accumbens dopamine tone causes sensorimotor gating failure, similar to that seen in schizophrenic patients. The time course of the observed schizophrenic and animal model deficits is compatible with the "temporal map" of monoaminergic neuron functions (ie, several hundred miliseconds). Studies of sensorimotor gating allow investigators to comment on the spatial and temporal mapping of neurons, trait and state deficits, and vulnerability factors in the schizophrenic spectrum of disorders. By translating attentional theories into testable hypotheses, the neurobiology of schizophrenic disorders becomes clearer.

Prestimulus Effects on Human Startle Reflex in Normals and Schizophrenics

Abstract: Graham (1975) demonstrated that a weak prestimulus could effectively inhibit or facilitate the eyeblink component of the startle reflex in humans, depending on the temporal duration of the prestimulus. This study had three goals: 1) to replicate the findings of Graham, 2) to establish the reliability of this phenomenon by a test-retest comparison, and 3) to compare the eyeblink reflex response of normal subjects with schizophrenic subjects. Seven prestimulus durations of continuous tone (from 0 to 2000 msec) were presented to 20 normal subjects and the results confirmed that maximal inhibition of eyeblink amplitude occurred in the 120 msec prestimulus condition. Increased amplitude occurred nonsignificantly when the prestimulus lasted for 2000 msec. On retest, 14 normal subjects showed a significant degree of reliability. When 20 normal subjects were compared to 12 schizophrenic subjects, significant differences in eyeblink response were found for blink amplitude and latency in the 60 msec prestimulus condition. This change is consistent with information processing “overload” theories of sensory overstimulation in schizophrenia. The blink reflex is a rather stable phenomenon and is probably altered in schizophrenia and/or by antipsychotic medication.