Effects of phencyclidine on prepulse inhibition of acoustic startle response in the macaque

Javitt, Daniel C.; Lindsley, Robert W.

doi:10.1007/s002130100758

Cited by 35 publications

(25 citation statements)

References 2 publications

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“…First, the effective interstimulus interval for inhibition in fish is comparable with previously reported effective lead intervals in humans (Braff et al, 1978), rats (Parisi and Ison, 1979;Mansbach and Geyer, 1991), and primates (Javitt and Lindsley, 2001). Second, as in higher vertebrates, prepulse inhibition in fish is modulated by dopaminergic and glutamatergic drugs.…”

Section: Discussionsupporting

confidence: 80%

Sensorimotor Gating in Larval Zebrafish

Burgess

Granato²

2007

J. Neurosci.

466

671

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Control of behavior in the natural environment where sensory stimuli are abundant requires superfluous information to be ignored. In part, this is achieved through selective transmission, or gating of signals to motor systems. A quantitative and clinically important measure of sensorimotor gating is prepulse inhibition (PPI) of the startle response, impairments in which have been demonstrated in several neuropsychiatric disorders, including schizophrenia. Here, we show for the first time that the acoustic startle response in zebrafish larvae is modulated by weak prepulses in a manner similar to mammalian PPI. We demonstrate that, like in mammals, antipsychotic drugs can suppress disruptions in zebrafish PPI induced by dopamine agonists. Because genetic factors underlying PPI are not well understood, we performed a screen and isolated mutant lines with reduced PPI. Analysis of Ophelia mutants demonstrates that they have normal sensory acuity and startle performance, but reduced PPI, suggesting that Ophelia is critical for central processing of sensory information. Thus, our results provide the first evidence for sensorimotor gating in larval zebrafish and report on the first unbiased screen to identify genes regulating this process.

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Section: Discussionsupporting

confidence: 80%

Sensorimotor Gating in Larval Zebrafish

Burgess

Granato²

2007

J. Neurosci.

466

671

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“…(cf. Braff et al 2001;Swerdlow et al 1994); this notion has been supported in recent years by findings of parallel effects of drugs (Javitt and Lindsley 2001;Linn and Javitt 2001), brain insults, and genetic abnormalities (Carter et al 1999;Kodsi and Swerdlow 1995;Swerdlow et al 1995) on PPI in rodents and primates. Each of the drugs tested in the present study reduces PPI in rodents, with varying degrees of potency and time courses .…”

Section: Discussionmentioning

confidence: 86%

Dopamine agonist effects on startle and sensorimotor gating in normal male subjects: time course studies

et al. 2002

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“…In primates, NMDAR antagonists also produce working memory 68,69 and PPI [70][71][72] deficits, supporting the relevance of glutamate receptors as therapeutic targets in schizophrenia.…”

Section: Animal Modelsmentioning

confidence: 78%

Glutamate as a therapeutic target in psychiatric disorders

2004

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Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Glutamatergic neurotransmission may be modulated at multiple levels, only a minority of which are currently being exploited for pharmaceutical development. Ionotropic receptors for glutamate are divided into N-methyl-D-aspartate receptor (NMDAR) and AMPA receptor subtypes. NMDAR have been implicated in the pathophysiology of schizophrenia. The glycine modulatory site of the NMDAR is currently a favored therapeutic target, with several modulatory agents currently undergoing clinical development. Of these, the full agonists glycine and D-serine have both shown to induce significant, large effect size reductions in persistent negative and cognitive symptoms when added to traditional or newer atypical antipsychotics in double-blind, placebo-controlled clinical studies. Glycine (GLYT1) and small neutral amino-acid (SNAT) transporters, which regulate glycine levels, represent additional targets for drug development, and may represent a site of action of clozapine. Brain transporters for D-serine have recently been described. Metabotropic glutamate receptors are positively (Group I) or negatively (Groups II and III) coupled to glutamatergic neurotransmission. Metabotropic modulators are currently under preclinical development for neuropsychiatric conditions, including schizophrenia, depression and anxiety disorders. Other conditions for which glutamate modulators may prove effective include stroke, epilepsy, Alzheimer disease and PTSD. Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Approximately 60% of neurons in the brain, including all cortical pyramidal neurons and thalamic relay neurons, utilize glutamate as their primary neurotransmitter. 1 As a result, virtually all thalamocortical, corticocortical and corticofugal neurotransmission in the brain is mediated by glutamate. Glutamate is released from presynaptic terminals in response to neuronal depolarization, and is recycled by excitatory amino acid (EAA) transporters located on both neurons and glia. 2 Within glia, glutamate is converted to glutamine and released into extracellular fluid from which it is reabsorbed into presynaptic terminals and converted back to glutamate via action of neuronal glutaminase. Up to 2/3 of brain energy metabolism is related to reuptake and recycling of glutamate. 3 As such, functional imaging modalities, such as PET and fMRI, indexing activity primarily of brain glutamatergic systems. 4 The exchange of glutamine from glia to neurons is accomplished by coordinated actions of two transport systems, systems N and A, both of which are members of sodium-dependent neutral amino acid (SNAT) family of transporters. 5 These transport systems also transport precursors for cysteine and glycine, which are precursors to glutathione synthesis. 6 As these transporters are electrogenic, glutamate transporters may also participate in cellular signaling. 7 As with glutamate and GABA transporters, these recycling systems may constitute interesti...

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Effects of phencyclidine on prepulse inhibition of acoustic startle response in the macaque

Abstract: These results demonstrate that both amplitude reduction and latency facilitation are observed during PPI in the monkey and are disrupted by PCP.

Cited by 35 publications

References 2 publications

Sensorimotor Gating in Larval Zebrafish

Sensorimotor Gating in Larval Zebrafish

Dopamine agonist effects on startle and sensorimotor gating in normal male subjects: time course studies

Glutamate as a therapeutic target in psychiatric disorders

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