Dopaminergic stimulation disrupts sensorimotor gating in the rat

Mansbach, Robert S.; Geyer, Mark A.; Braff, David L.

doi:10.1007/bf00212846

Cited by 585 publications

(419 citation statements)

References 24 publications

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“…Percentage scores were used in order to minimize the effect of individual variation of startle amplitude on PPI (Mansbach et al 1988). Using this description of PPI, a high degree of sensorimotor gating is reflected in a high % PPI value, whereas less or no gating results in a small or negative % PPI value.…”

Section: Discussionmentioning

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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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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Section: Discussionmentioning

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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“…For the scopolamine-reversal studies, scopolamine HBr (Sigma S1875) 0.33 mg/kg was administered 40 min before testing followed by either vehicle or AChEI 20 min before testing. The PPI methods and the compounds used to disrupt PPI (and their doses) were based on earlier studies (Mansbach et al, 1988;Mansbach and Geyer, 1989;Jones and Shannon, 2000b) and recent work in our laboratory (Terry et al, 2005). Galantamine was tested at doses of 0.3, 1.0, and 3.0 mg/kg while donepezil doses were 0.5, 1.0, and 2.0 mg/kg.…”

Section: Drugsmentioning

confidence: 99%

“…Accordingly, a number of animal models of PPI impairment have been developed which include neonatal ventral hippocampal lesion, maternal deprivation, isolation rearing, genetic, and pharmacological models, the later being commonly used in antipsychotic drug development studies . Such pharmacological models have provided evidence that the neurotransmitters dopamine (Mansbach et al, 1988), glutamate (Mansbach and Geyer, 1989), serotonin (Sipes and Geyer, 1994), and acetylcholine (Jones and Shannon, 2000), are each likely to play an important role in normal sensory gating and PPI as well as disorders of these processes.…”

Section: Introductionmentioning

confidence: 99%

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats

2007

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Acetylcholinesterase inhibitors (AChEIs) are currently being evaluated as adjunctive therapy for the cognitive dysfunction of schizophrenia. This core symptom of schizophrenia has often been attributed to impaired attention and abnormal sensory motor gating, features that are also found in Huntington's Disease, autism, and several other psychiatric and neurological disorders. The ability to improve prepulse inhibition (PPI) of the acoustic startle response may predict the efficacy of compounds as cognitive enhancers. In this study, PPI was disrupted in Wistar rats in three pharmacologic models: dopamine receptor agonism by apomorphine, NMDA receptor antagonism by MK-801, or muscarinic acetylcholine receptor antagonism by scopolamine. We then evaluated the commonly used AChEIs, donepezil (0.5, 1.0, or 2.0 mg/kg) and galantamine (0.3, 1.0, or 3.0 mg/kg) for the capacity to improve PPI in each model. Under vehicle conditions, the prepulse stimuli (75, 80 and 85 dB) inhibited the startle response to a 120 dB auditory stimulus in a graded fashion. Galantamine (depending on dose) improved PPI deficits in all three PPI disruption models, whereas donepezil ameliorated PPI deficits induced by scopolamine and apomorphine, but was not effective in the MK801 model. These results indicate that some AChEIs may have the potential to improve cognition in schizophrenia by improving auditory sensory gating.

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“…A high-frequency loudspeaker inside the chamber produced both a continuous background noise of 65 dB and the various acoustic stimuli. As described previously (Mansbach et al, 1988), the whole-body startle response of the animal caused vibrations of the Plexiglas cylinder, which were then converted into analog signals by a piezoelectric unit attached to the platform. These signals were digitized and stored by a microcomputer and interface unit.…”

Section: Microinfusion Proceduresmentioning

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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Dopaminergic stimulation disrupts sensorimotor gating in the rat

Cited by 585 publications

References 24 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

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats

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

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