Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: Effects of antipsychotics and other agents in rats

Johansson, Christina; Jackson, David M.; Zhang, Jianhua; Svensson, Lennart

doi:10.1016/0091-3057(95)00160-x

Cited by 137 publications

(99 citation statements)

References 31 publications

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“…In addition, direct infusion of DOI (1.0-10.0 mg/0.5 ml) into the ventral pallidum or the nucleus accumbens, which are important in the modulation of PPI, also did not change startle reactivity (Sipes and Geyer, 1997). Only high doses of the 5-HT 2A/2C agonists DOI (42 mg/kg) and DOB (3 mmol/kg) reduced startle amplitude in rats (Johansson et al, 1995;Padich et al, 1996).…”

Section: Discussionmentioning

confidence: 87%

“…It is also of note that the partial 5-HT 1A agonist buspirone increased PPI in rats (Johansson et al, 1995), despite the many reports that more specific and full 5-HT 1A agonists disrupt PPI in rats (for review see Geyer et al (2001)). Thus, it might be possible that psilocybin, particularly with increasing doses, leads to an additional stimulation of 5-HT 1A receptors which in turn may have masked (at 60 ms) or counteracted (at 120-240 ms) potential 5-HT 2A receptor-mediated PPI deficits at longer ISIs.…”

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confidence: 99%

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The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Vollenweider

Csomor

Knappe

et al. 2007

Neuropsychopharmacol

153

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Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT 2A receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT 2A receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 mg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dosedependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Vollenweider

Csomor

Knappe

et al. 2007

Neuropsychopharmacol

153

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“…Acute administration of DA agonists such as cocaine, amphetamine, and apomorphine increases startle amplitude in rats (Kehne and Sorenson 1978;Davis 1980;Johansson et al 1995;see Martinez et al 1999), presumably as a result of increased DA neurotransmission. Acute administration of DA antagonists such as haloperidol or clozapine depress startle amplitude (Mansbach et al 1988;Johansson et al 1995). Since we tested only acoustic startle, it is unknown at present whether our results would be generalizable to other sensory modalities.…”

Section: Discussionmentioning

confidence: 99%

“…This response is sensitive to dopaminergic modulation. Direct and indirect DA agonists, such as apomorphine, cocaine and d-amphetamine, increase startle amplitude in animals (Kehne and Sorenson 1978;Davis 1980;Johansson et al 1995), whereas DA antagonists such as haloperidol and clozapine reduce startle amplitude (Mansbach et al 1988;Johansson et al 1995 The acoustic startle response can be attenuated if a weak, non-startling prestimulus (a prepulse) immediately precedes the startle stimulus (Graham 1975;Braff et al 1992). This phenomenon is known as prepulse inhibition of startle (PPI), the pharmacology of which has been well characterized in animal studies.…”

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confidence: 99%

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Diminished Acoustic Startle in Chronic Cocaine Users

Efferen

Duncan

Szilágyi

et al. 2000

Neuropsychopharmacology

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Chronic cocaine use has been shown to produce neurochemical alterations which persist after acute withdrawal. This study assessed the effects of cocaine use on the acoustic startle response and sensorimotor gating using prepulse inhibition (PPI) Chronic cocaine use causes physiological and neurochemical alterations which persist well after drug cessation. At the commencement of abstinence, adaptive decreases in dopamine (DA) receptor density (Kleven et al. 1990;Laurier et al. 1994) and DA uptake (Izenwasser and Cox 1990), as well as increases in DA transporter (DAT) mRNA expression (Pilotte et al. 1994;Wamsley and Alburges 1993) and cocaine binding sites (Malison et al. 1998), have been reported. As abstinence continues, there are decreases in basal DA efflux (Parsons et al. 1991;Weiss et al. 1992), DAT mRNA expression (Pilotte et al. 1994), DAT in nucleus accumbens (Wilson et al. 1994), and D 1 receptor density (Kleven et al. 1990), leading to an overall state of decreased dopaminergic neurotransmission (Kuhar and Pilotte 1996).The acoustic startle response under observation in this study is a well characterized response consisting of a reflexive contraction of the skeletal musculature in response to an intense, abrupt stimulus. It is mediated by a simple 3-synapse subcortical circuit Koch et al. 1993). In humans, the response is quantified using electromyographic (EMG) measurements of the obicularis oculi facial muscle (Hoffman and Searle 1968). This response is sensitive to dopaminergic modulation. Direct and indirect DA agonists, such as apomorphine, cocaine and d-amphetamine, increase startle amplitude in animals (Kehne and Sorenson 1978;Davis 1980;Johansson et al. 1995), whereas DA antagonists such as haloperidol and clozapine reduce startle amplitude (Mansbach et al. 1988;Johansson et al. 1995 The acoustic startle response can be attenuated if a weak, non-startling prestimulus (a prepulse) immediately precedes the startle stimulus (Graham 1975;Braff et al. 1992). This phenomenon is known as prepulse inhibition of startle (PPI), the pharmacology of which has been well characterized in animal studies. Dopamine agonists, both direct and indirect, reduce or eliminate PPI; D2 antagonists reverse the effect of agonists such as apomorphine (Mansbach et al. 1988). On the other hand, D1 antagonism fails to reverse the effect (Swerdlow et al. 1991).The aim of the present study was to examine the functional consequences of long-term cocaine use by studying the acoustic startle response and PPI of the acoustic startle response during abstinence following prolonged cocaine use. MATERIALS AND METHODS SubjectsSixty cocaine subjects and 20 normal individuals were screened in consideration for participation. Nine healthy male normal controls and 15 male cocaine users were enrolled in the study after signing a VA/NYU IRB approved consent form.All subjects were screened to rule out presence or history of psychiatric or medical pathology (excluding substance induced disorders for the cocaine users) using the Structured Cli...

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Dendritic morphology of neurons in prefrontal cortex and ventral hippocampus of rats with neonatal amygdala lesion

Vázquez-Roque

Solís

Camacho-Ábrego

et al. 2012

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Neonatal basolateral amygdala (nBLA) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Recently, we reported that nBLA lesions result in significant decreases in the dendritic spine number of layer 3 prefrontal cortex (PFC) pyramidal cells and medium spiny neurons of the nucleus accumbens (NAcc), which all changes after puberty. At present, we aimed to evaluate the effect of this lesion in pyramidal neurons of CA1 of the ventral hippocampus (VH) and layer 5 of the PFC. In order to assess the effects of nBLA lesions on the dendritic morphology of the PFC and VH neurons, we carried out nBLA lesions in rats on postnatal day (PD) 7, and then we studied the dendritic morphology of these two limbic subregions at prepubertal (PD35) and postpubertal (PD60) ages. Dendritic characteristics were measured by Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of nBLA lesions on the prepulse inhibition (PPI) and acoustic startle responses. The nBLA lesion induced a significant increase in dendritic length of layer 5 pyramidal neurons of the PFC at both ages, with a decrease in the dendritic spines density after puberty. The spine density of CA1 VH pyramidal neurons showed significant decreases at both ages. PPI was decreased in adulthood in the animals with an nBLA lesion. These results show that an nBLA lesion alters the dendritic morphology at the level of the PFC and VH in distinct ways before puberty, suggesting a disconnection between these limbic structures at an early age, and increasing our understanding of the implications of the VH in early amygdala dysfunction in schizophrenia.

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Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: Effects of antipsychotics and other agents in rats

Cited by 137 publications

References 31 publications

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Diminished Acoustic Startle in Chronic Cocaine Users

Dendritic morphology of neurons in prefrontal cortex and ventral hippocampus of rats with neonatal amygdala lesion

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