Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats

Rasmussen, Bruce A.; O’Neil, Jahn N.; Manaye, Kebreten F.; Perry, David C.; Tizabi, Yousef

doi:10.1007/s00213-006-0584-z

Cited by 36 publications

(27 citation statements)

References 30 publications

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“…This result is parallel to our recent finding of long-term changes in sensorimotor gating in a developmental PCP model (Rasmussen et al, 2007). Previous studies have not found longterm PPI impairments with chronic NMDA antagonism.…”

Section: Discussionsupporting

confidence: 88%

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Effects of nicotine on sensorimotor gating impairment induced by long-term treatment with neurotoxic NMDA antagonism

et al. 2008

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In order to develop a model of persistent sensorimotor gating that did not require acute NMDA (N-methyl-D-aspartate) receptor blockade, adult female Sprague-Dawley rats were pre-treated with N-methyl-scopolamine (1 mg/kg s.c.), then administered MK-801 (dizocilpine, 5 mg/kg i.p.) along with two separate doses (5 mg/kg) of pilocarpine. The drug regimen was repeated four and eight days later. Controls received saline in lieu of any drug. Ten days after the last neurotoxic treatment, rats had a significant impairment (reduction) in pre-pulse inhibition (PPI). Each treatment group (neurotoxic treated and control) was then divided into two groups for treatment with saline or 0.5 mg/kg nicotine, administered s.c. twice daily from days 10 to 23. The rats were tested for sensorimotor gating on days 17 and 22 shortly after the morning nicotine administration. Nicotine did not affect the PPI in control animals. On day 17, PPI impairment was sustained in neurotoxically treated rats, regardless of saline or nicotine treatment. On day 22, however, the effect of neurotoxic treatment on PPI was totally absent in saline treated rats, whereas in nicotine treated rats, PPI impairment was still evident. Combination of nicotine and neurotoxic treatment also caused an up-regulation of high affinity nicotinic receptors in the cortex and the thalamus and apparent normalization of low affinity nicotinic receptors in the hippocampus. The findings indicate that muscarinic activation, in conjunction with neurotoxic NMDA receptor antagonism, produces relatively long-term impairment in auditory gating, a result relevant to modeling clinical observations of schizophrenia-associated symptoms. Contrary to expectation, nicotine administration in this model resulted in further impairment rather than amelioration of PPI. The results suggest a sustainable model of PPI impairment and possible role of nicotinic receptors in selective brain regions in this behavior.

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Section: Discussionsupporting

confidence: 88%

“…This protocol was based on our recently completed study and utilized 24 paired and 24 unpaired auditory stimuli presented in pseudo-random order with 20-40 seconds between trials (Rasmussen et al, 2007). The acclimation period in the chambers before data acquisition was 3 minutes.…”

Section: Sensorimotor Gatingmentioning

confidence: 99%

Effects of nicotine on sensorimotor gating impairment induced by long-term treatment with neurotoxic NMDA antagonism

et al. 2008

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“…However, a study has reported that neurotoxic doses of PCP and MK-801 did not result in enduring behavioral changes in social interactions when tested 7 to 10 days after the drug administration (Sams-Dodd, 2004). Rasmussen et al (2007) also observed a transient effect of PCP on measures of sensorimotor gating when it was given during the developmental period, a finding that is consistent with the reports of Martinez et al (1999) and Becker et al (2003) who noted that the auditory gating was disrupted only during the actual presence of NMDA receptor antagonists. Hence, behavioral effects of NMDA antagonists may require the presence of adequate concentration of the antagonist in the body.…”

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confidence: 69%

“…In rodents, however, this "gating" is typically assessed by measuring prepulse inhibition of the acoustic startle response using a strain gauge apparatus. Thus, the ASR is reduced when it is preceded by a smaller neutral tone, typically to 40-70% of the original ASR (see Geyer 2006;Rasmussen et al, 2007). f It is now well established that administration of Y. TIZABI 236 the NMDA receptor antagonists result in disruption of PPI in mice and rats.…”

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confidence: 97%

Nicotine and nicotinic system in hypoglutamatergic models of schizophrenia

Tizabi

2007

neurotox res

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Schizophrenia is a complex neuropsychiatric disorder with devastating consequences. It is characterized by thought fragmentation, hallucination and delusion, collectively referred to as positive symptoms. In addition, mood changes or affective disorders, referred to as negative symptoms, as well as cognitive impairments can be manifested in these patients. Arguably, modeling such a disorder in its entirety in animals might not be feasible. Despite this limitation, various models with significant construct, predictive and some face validity have been developed. One such model, based on hypoglutamatergic hypothesis of schizophrenia, makes use of administering NMDA receptor antagonists and evaluating behavioral paradigms such as sensorimotor gating. Because of very high incidence of smoking among schizophrenic patients, it has been postulated that some of these patients may actually be self medicating with tobacco's nicotine. Research on nicotinic-glutamatergic interactions using various animal models has yielded conflicting results. In this review, some of these models and possible confounding factors are discussed. Overall, a therapeutic potential for nicotinic agonists in schizophrenia can be suggested. Moreover, it is evident that various experimental paradigms or models of schizophrenia symptoms need to be combined to provide a wider spectrum of the behavioral phenotype, as each model has its inherent limitations.

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“…18 In animal models, gultamatergic antagonists, such as PCP, disrupt PPI, spatial learning and social interaction. 135,137,[139][140][141] Increased locomotion and stereotyped behaviour were also evident in rats treated with single and repeated doses of PCP. 107,142,143 The social interaction deficits and stereotypy caused by PCP administration were reversed by conventional and novel antipsychotic medications.…”

Section: Pharmacologic Animal Modelsmentioning

confidence: 96%

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

Lazar

Neufeld²,

Cain³

2011

jpn

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Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats

Abstract: These data suggest that treatment with an NMDA receptor antagonist during adolescence or early adulthood can produce a relatively long-term impairment of PPI (approximately 1 week) and that this effect is more pronounced in male animals.

Cited by 36 publications

References 30 publications

Effects of nicotine on sensorimotor gating impairment induced by long-term treatment with neurotoxic NMDA antagonism

Effects of nicotine on sensorimotor gating impairment induced by long-term treatment with neurotoxic NMDA antagonism

Nicotine and nicotinic system in hypoglutamatergic models of schizophrenia

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

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