Effects of Sustained Phencyclidine Exposure on Sensorimotor Gating of Startle in Rats

Martinez, Z.A.; Ellison, Gaylord; Geyer, Mark A.; Swerdlow, Neal R.

doi:10.1016/s0893-133x(98)00137-7

Cited by 67 publications

(41 citation statements)

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“…PCP doses of 10-20 mg/kg/day in rodents have also been found to be effective by other groups (Jentsch et al, 1998a;Martinez et al, 1999;Sams-Dodd, 1998). Ehrhardt et al (1999) found no significant effect of 5 mg/kg/day PCP, similar to the observations in the present study.…”

Section: Discussionsupporting

confidence: 91%

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

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Serra

et al. 2003

Neuropsychopharmacol

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Functional dopaminergic hyperactivity is a key feature of schizophrenia. Etiology of this dopaminergic hyperactivity, however, is unknown. We have recently demonstrated that subchronic phencyclidine (PCP) treatment in rodents induces striatal dopaminergic hyperactivity similar to that observed in schizophrenia. The present study investigates the ability of PCP to potentiate amphetamine-induced dopamine release in prefrontal cortex (PFC) and nucleus accumbens (NAc) shell. Prefrontal dopaminergic hyperactivity is postulated to underlie cognitive dysfunction in schizophrenia. In contrast, the degree of NAc involvement is unknown and recent studies have suggested that PCP-induced hyperactivity in rodents may correlate with PFC, rather than NAc, dopamine levels. Rats were treated with 5-20 mg/kg/day PCP for 3-14 days by osmotic minipump. PFC and NAc dopamine release to amphetamine challenge (1 mg/kg) was monitored by in vivo microdialysis and HPLC-EC. Doses of 10 mg/kg/day and above produced serum PCP concentrations (50-150 ng/ml) most associated with PCP psychosis in humans. PCP-treated rats showed significant, dose-dependent enhancement in amphetamine-induced dopamine release in PFC but not NAc, along with significantly enhanced locomotor activity. Enhanced response was observed following 3-day, as well as 14-day, treatment and resolved within 4 days of PCP treatment withdrawal. These findings support the concept that endogenous NMDA receptor dysfunction could account for the pattern of dopaminergic dysfunction observed in schizophrenia, and suggest that even short duration abuse of PCP-like agents may greatly potentiate behavioral effects of psychostimulants in drug abuse situations. Finally, these studies provide a model system in which to evaluate effects of potential psychotherapeutic agents.

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Section: Discussionsupporting

confidence: 91%

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

Balla

Sershen

Serra

et al. 2003

Neuropsychopharmacol

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“…It has been thought that cortical, pallidal, striatal, and thalamic neuronal circuits have important roles for mediating the PPI paradigm. It has been indicated that psychotomimetic drugs such as dopaminergic agonists such as amphetamine and apomorphine, and glutamatergic NMDA receptor antagonists such as MK-801 and PCP induce PPI deficits via their acute effects and the effects are commonly transient [8,35]. In our study, we demonstrated that MK-801 administration induced PPI impairments and agmatine treatment did not ameliorate the disruptive effect of MK-801.…”

Section: Discussioncontrasting

confidence: 42%

“…Acute injection of these antagonists is commonly used for modelling psychosis-like behaviours, while low-dose subchronic administrations (generally twice a day for seven days) create long-lasting negative and cognitive symptoms in rodents [6]. Studies showed that both acute and chronic administration of NMDA receptor antagonists disrupted prepulse inhibition paradigm, which is considered as an important marker for schizophrenia [7,8].…”

Section: Introductionmentioning

confidence: 99%

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Ünal

Ateş

Arıcıoğlu

2018

Psychiatry and Clinical Psychopharmacology

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INTRODUCTION: Schizophrenia is one of the most severe psychiatric disorders with about 1% prevalence. It has been proved that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists such as MK-801 and phencyclidine cause schizophrenia-like behaviours in rodents. Agmatine is an endogenous amine synthesized from decarboxylation of arginine and has been thought to be a neurotransmitter/neuromodulator. It binds to imidazoline and alfa adrenergic receptors and blocks cation channelled receptors, such as nicotinic acetylcholine, 5-HT3 serotonergic, and NMDA receptors. It is an endogenous inhibitor of nitric oxide synthase. A limited number of studies showed that agmatine attenuates sensorimotor gating deficit, which is an important parameter for schizophrenia, and improves cognitive deficits in rats. Despite this, it has also been shown that high doses of agmatine impaired sensorimotor gating. Herein, the aim of our study is to investigate the effect of subchronic agmatine treatment on sensorimotor gating, visual recognition memory, and social functions in subchronic MK-801 model of schizophrenia in rats. METHODS: Wistar Hannover rats were divided into four groups as control (dimethyl sulphoxide), MK-801 (0.2 mg/kg), MK-801 + agmatine (20 mg/kg), and MK-801 + risperidone (0.5 mg/kg)(n = 8 per group). MK-801 was subcutaneously injected once a day for 14 days. Agmatine and risperidone were administered intraperitoneally in the last seven days of MK-801 injections. On day 14, agmatine or risperidone was injected 15 minutes before MK-801 and MK-801 15 minutes before prepulse inhibition of the acoustic startle response (PPI) test. After the seven days washout period, social interaction (SI) test and novel object recognition test (NORT) were performed. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical evaluation of NORT, SI, and PPI, respectively. Paired Student's t-test was used for the comparison of rat's affinity to a familiar and novel object in NORT. RESULTS: MK-801 administration significantly decreased prepulse inhibition of rats in the PPI test (p < .001). In addition to this, MK-801 decreased startle response to pulse-alone trials and increased basal activity measured by the magnitude of no stimulus trials compared to the control group (p < .05). Agmatine treatment did not improve MK-801-induced PPI, startle response, or basal activity deficits while risperidone blocked the disruptive effect of MK-801 (p < .05). In NORT, the MK-801 group had significantly lower discrimination index (p < .05), whereas both the agmatine and risperidone treatments substantially increased this index (p < .01). Moreover, MK-801 injections not only decreased sniffing (p < .01) and following (p < .01) behaviours but also increased avoiding behaviour (p < .001) in SI. Agmatine partially treated social deficits (p < .001) while risperidone was reversed all of them (p < .01). CONCLUSIONS: Subchronic MK-801 administration revealed sensorimotor gating, social and cognitive deficits in rats. Subchroni...

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“…All acoustic startle experiments were conducted in an acoustic startle chamber (SR-LAB; San Diego Instruments, San Diego, CA, USA). Two days before treatment inception, a brief startle session was performed to obtain experimental and control groups matched for startle reactivity (matching session; Geyer and Swerdlow, 1998;Martinez et al, 1999). In all experimental groups, PPI test was conducted at day 10 (2 days after CEF withdrawal) to allow complete clearance of the antibiotic (Rebuelto et al, 2003), 30 min after the injection of saline or LY379268.…”

Section: Ppi Of the Startle Reflexmentioning

confidence: 99%

The mGluR2/3 Agonist LY379268 Blocks the Effects of GLT-1 Upregulation on Prepulse Inhibition of the Startle Reflex in Adult Rats

Bellesi

Conti

2010

Neuropsychopharmacol

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The main glutamate transporter GLT-1 is responsible for clearing synaptically released glutamate from the extracellular space and contributes to the shaping of glutamatergic transmission. Recently, it has been shown that ceftriaxone (CEF)-induced GLT-1 upregulation is associated with an impairment of the prepulse inhibition (PPI) of the startle reflex, a simple form of information processing that is reduced in schizophrenia, and determines a strong reduction in hippocampal metabotropic glutamate receptor (mGluR)2/3-dependent long-term depression. In this study, we tested the hypothesis that administration of the mGluR2/3 agonist LY379268 blocks the effect of GLT-1 upregulation on PPI of the startle. We showed that administration of LY379268 (1 mg/kg) prevented PPI alterations associated with GLT-1 upregulation, suggesting that CEF-induced PPI impairment was mGluR2/3 dependent. In addition, we showed that CEF-induced GLT-1 upregulaton did not alter the expression of mGluR2/3, and also that it occurred at sites of mGluR2/3 expression. These results indicate a novel mechanism by which GLT-1 upregulation modulates PPI of the startle.

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Effects of Sustained Phencyclidine Exposure on Sensorimotor Gating of Startle in Rats

Abstract: Phencyclidine (PCP), a non-competitive

Cited by 67 publications

References 50 publications

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

The mGluR2/3 Agonist LY379268 Blocks the Effects of GLT-1 Upregulation on Prepulse Inhibition of the Startle Reflex in Adult Rats

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