Prestimulus Effects on Human Startle Reflex in Normals and Schizophrenics

Braff, David L.; Stone, C.; Callaway, Enoch; Geyer, Mark A.; Glick, Ira; Bali, Likh

doi:10.1111/j.1469-8986.1978.tb01390.x

Cited by 1,126 publications

(695 citation statements)

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“…In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in (Braff et al 1978;Kumari et al 1999). A well-established sensorimotor gating paradigm is the prepulse inhibition (PPI) of the startle response.…”

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confidence: 56%

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Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Borrell

Vela²,

Arévalo-Martı́n³

et al. 2002

Neuropsychopharmacology

280

191

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Increasing evidence associates schizophrenia with prenatal exposure to infection. Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) of the acoustic startle reflex. We analyzed the effect of a prenatal immune challenge-peripheral administration of bacterial endotoxin lipopolysaccharide (LPS) to pregnant female rats-upon PPI and immune function in adult offspring. Prenatal LPS treatment disrupted PPI which was reversed by antipsychotics. Serum levels of interleukin-2 and interleukin-6 were increased. In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in (Braff et al. 1978;Kumari et al. 1999). A well-established sensorimotor gating paradigm is the prepulse inhibition (PPI) of the startle response. PPI refers to the reduction in startle reactivity toward an intense pulse stimulus when it is shortly preceded by a weak prepulse stimulus (Hoffman and Ison 1980). It is thought that the prepulse response activates an inhibitory process that attenuates or "gates" the startle response. Because identical stimulus parameters can be used for animal and human studies, it is considered that animal models of PPI disruption represent a promising way to study the neural mechanisms underlying sensorimotor gating dysfunction (Swerdlow et al. 1994(Swerdlow et al. , 1999Swerdlow and Geyer 1998) and as a screening test for potential antipsychotics (Swerdlow et al. 1994;Depoortere et al. 1997). In fact, antipsychotics remove PPI deficits in schizophrenic patients (Kumari et al. 1999;Weike et al. 2000). Nevertheless, it must be taken into consideration that deficiency of PPI has been reported in other selected neuropsychiatric disorders where inability to inhibit movements is involved (Huntington's disease (Swerdlow et al. 1995 Tourette's syndrome (Castellanos et al. 1996)), where inability to control attentional and cognitive processes is involved (obsessive-compulsive disorder (Swerdlow et al. 1993)), or where anxiety and exaggerated startle occur (posttraumatic stress disorder (Grillon et al. 1996)). The focus of schizophrenia research has been turning from studies of structural and functional brain abnormalities to an increasing emphasis on possible etiologic factors. Neurodevelopmental theories of schizophrenia postulate that the psychopathology of schizophrenia may derive from alterations of brain organization secondary to defective ontogenesis (Weinberger 1996;Raedler et al. 1998). A causal relationship pertaining to disturbed brain ontogenesis and schizophrenia comes from epidemiological studies that have identified several risk factors that, acting during pregnancy, increase the incidence of the disease in offspring. Maternal infection with influenza virus in the second trimester of preg...

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confidence: 56%

“…Pronounced sensorimotor gating abnormalities have been reported in schizophrenic patients (Braff et al 1978;Kumari et al 1999). A well-established sensorimotor gating paradigm is the prepulse inhibition (PPI) of the startle response.…”

mentioning

confidence: 99%

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Borrell

Vela²,

Arévalo-Martı́n³

et al. 2002

Neuropsychopharmacology

280

191

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“…PPI refers to the normal diminution of the startle response when the startling stimulus is preceded immediately by a weak intensity prepulse, and is deficient in a number of psychiatric illnesses that involve disturbed sensorimotor gating, including schizophrenia (Braff et al, 1978;Hoffman and Ison, 1980;Ison and Hoffman, 1983). Sensorimotor gating, as indexed by PPI, represents an important form of preattentional information processing that is critical for the maintenance of selective attention and normal cognitive functioning (Braff and Light, 2004).…”

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confidence: 99%

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Alsene

Carasso²,

Connors

et al. 2006

Neuropsychopharmacol

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Prepulse inhibition (PPI) refers to the attenuation of startle when a weak prestimulus precedes the startling stimulus. PPI is deficient in several psychiatric illnesses involving poor sensorimotor gating. Previous studies indicate that a1 adrenergic receptors regulate PPI, yet the extent to which these effects are mediated by central vs peripheral receptors is unclear. The present studies compared the effects of intracerebroventricular (ICV) vs intraperitoneal (IP) delivery of several a1 receptor agonists on PPI. Male Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 mg/5 ml), methoxamine (0, 30, 100 mg/5 ml), or phenylephrine (0, 3, 10, 30 mg/5 ml) ICV immediately before testing. Separate groups received either cirazoline (0, 0.25, 0.50, 0.75 mg/kg), methoxamine (0, 2, 5, 10 mg/kg), or phenylephrine (0, 0.1, 2.0 mg/kg) IP 5 min before testing. PPI, baseline startle responses, and piloerection, an index of autonomic arousal, were measured. Cirazoline disrupted PPI; effective ICV doses were approximately six times lower than effective IP doses. Methoxamine disrupted PPI after ICV infusion but failed to affect PPI with IP doses that were up to 30-fold higher than the effective ICV dose. Phenylephrine disrupted PPI with ICV administration, but did not alter PPI after IP injection of even a 20-fold higher dose. None of the ICV treatments altered baseline startle magnitude, but phenylephrine and methoxamine lowered startle after administration of high systemic doses. Piloerection was induced by cirazoline via either route of administration, and by IP methoxamine and phenylephrine, but not by ICV infusion of methoxamine or phenylephrine. These findings indicate that a1 receptor-mediated PPI disruption occurs exclusively through stimulation of central receptors and is dissociable from alterations in baseline startle or autonomic effects.

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“…Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is the reduction in startle amplitude that results when an abrupt startling stimulus is preceded 30-500 msec by a nonstartling prepulse (Graham 1975). Patients with several neuropsychiatric disorders, including schizophrenia (Braff et al 1978Bolino et al 1994), schizotypal personality disorder (Cadenhead et al 1993), and obsessive compulsive disorder (Swerdlow 1995) exhibit PPI deficits. Startle habituation, a simple form of learning, which refers to the decrement in startle responding to repeated presentations of an initially novel and intense stimulus (Thorpe 1956), is also deficient in schizophrenia and schizotypal patients Cadenhead et al 1993;Geyer and Braff 1982;Bolino et al 1994).…”

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confidence: 99%

Knockout Mice Reveal Opposite Roles for Serotonin 1A and 1B Receptors in Prepulse Inhibition

Dulawa

Gross

Stark

et al. 2000

Neuropsychopharmacology

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The serotonergic system is involved in the modulation of prepulse inhibition (PPI) Anpirtoline; 8-OH-DPAT; Flesinoxan; RU 24969 Sensorimotor gating is a form of central nervous system inhibition that "gates" or filters out excessive sensory, motor, and cognitive information to sustain mental and behavioral integration. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is the reduction in startle amplitude that results when an abrupt startling stimulus is preceded 30-500 msec by a nonstartling prepulse (Graham 1975). Patients with several neuropsychiatric disorders, including schizophrenia (Braff et al. 1978Bolino et al. 1994), schizotypal personality disorder (Cadenhead et al. 1993), and obsessive compulsive disorder (Swerdlow 1995) exhibit PPI deficits. Startle habituation, a simple form of learning, which refers to the decrement in startle responding to repeated presentations of an initially novel and intense stimulus (Thorpe 1956), is also deficient in schizophrenia and schizotypal patients Cadenhead et al. 1993;Geyer and Braff 1982;Bolino et al. 1994). Further investigation of the neural substrates modulating PPI may provide insight into the pathophysiology of the sensorimotor gating deficits in these syndromes.Serotonin 1A (5-HT 1A ) and serotonin 1B (5-HT 1B ) receptors have been suggested to contribute to the modulation of PPI. For instance, the 5-HT 1A agonist 8-OH-DPAT decreases PPI in rats (Rigdon and Weatherspoon 1992;Sipes and Geyer 1995), but increases PPI in mice (Dulawa et al. 1997(Dulawa et al. , 1998. However, 8-OH-DPAT also has affinity for 5-HT 7 receptors (Tsou et al. 1994;Ying and Rusak 1997 Received August 27, 1999; revised November 29, 1999; accepted December 6, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 6 Opposite Roles for 5-HT1A and 1B Receptors in Murine PPI 651 5-HT 1B knockout (1BKO) mice (Dulawa et al. 1997), suggesting that 5-HT 1B receptors modulate both forms of startle plasticity in mice.The recent availability of 5-HT 1A knockout (1AKO) mice (Ramboz et al. 1998;Heisler et al. 1998;Parks et al. 1998) and the selective 5-HT 1B agonist anpirtoline (Schlicker et al. 1992) permits more precise dissection of the roles of 5-HT 1A and 5-HT 1B receptors in behaviors of interest. 5-HT 1A receptors are autoreceptors and heteroreceptors for serotonergic and nonserotonergic neurons and are located on cell bodies and dendrites, where they inhibit cell firing (Hamon et al. 1990). 5-HT 1B receptors are autoreceptors and heteroreceptors expressed on axon terminals that inhibit neurotransmitter release (Boschert et al. 1994;Hen 1992). The densest localization of 5-HT 1A receptors is in the hippocampus, dorsal raphe, interpeduncular nucleus, and lateral septum (Ramboz et al. 1998). 5-HT 1B receptors are most densely localized on striatal neuron terminals in the globus pallidus and substantia nigra, and on Purkinje neuron terminals in the deep cerebellar nuclei (Boschert et al. 1994;Pazos et al. 1988). Many of these brain regions, such as the hippoca...

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Prestimulus Effects on Human Startle Reflex in Normals and Schizophrenics

Cited by 1,126 publications

References 8 publications

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Knockout Mice Reveal Opposite Roles for Serotonin 1A and 1B Receptors in Prepulse Inhibition

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