Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine

Schulz, Brigitte; Fendt, Markus; Pedersen, Vera; Koch, Michael

doi:10.1007/s002130100776

Cited by 32 publications

(19 citation statements)

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“…Because of the within-subject design used in these studies, one concern was that locomotor responses to MK-801 would change as a function of repeated exposure to the drug (Schulz et al, 2001). To address this concern, data from animals pretreated with saline and treated with one of the MK-801 doses were split into two test periods (n = 6 per period for each dose) according to the date of testing: the first days of testing vs. the last days of testing.…”

Section: Resultsmentioning

confidence: 99%

“…H 3 antagonists improve PPI in DBA/2 mice, a mouse strain that demonstrates deficient PPI (Browman et al, 2004), and reverse the debilitating effects of the dopamine agonist, apomorphine, on PPI (Ligneau et al, 2007a). While the ability of MK-801 to increase auditory startle and decrease PPI have been reported in numerous studies (Bakshi and Geyer 1998; Schulz et al, 2001; Bardgett et al, 2009), the effects of ciproxifan on PPI deficits induced by NMDA antagonists have not been reported. Using methods identical to those described by Swerdlow et al, (2000) who used them to assess differences in PPI between rat strains, the present study found that ciproxifan does not alter the disruptive effects of MK-801 on acoustic startle and PPI.…”

Section: Discussionmentioning

confidence: 99%

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The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats

et al. 2010

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Summary Antagonists of H3-type histamine receptors exhibit cognitive-enhancing properties in various memory paradigms as well as evidence of antipsychotic activity in normal animals. The present study determined if a prototypical H3 antagonist, ciproxifan, could reverse the behavioral effects of MK-801, a drug used in animals to mimic the hypoglutamatergic state suspected to exist in schizophrenia. Four behaviors were chosen for study, locomotor activity, ataxia, prepulse inhibition (PPI), and delayed spatial alternation, since their modification by dizocilpine (MK-801) has been well characterized. Adult male Long-Evans rats were tested after receiving a subcutaneous injection of ciproxifan or vehicle followed twenty minutes later by a subcutaneous injection of MK-801 or vehicle. Three doses of MK-801 (0.05, 0.1, & 0.3 mg/kg) increased locomotor activity. Each dose of ciproxifan (1.0 & 3.0 mg/kg) enhanced the effect of the moderate dose of MK-801, but suppressed the effect of the high dose. Ciproxifan (3.0 mg/kg) enhanced the effects of MK-801 (0.1 & 0.3 mg/kg) on fine movements and ataxia. Deficits in PPI were observed after treatment with MK-801 (0.05 & 0.1 mg/kg), but ciproxifan did not alter these effects. Delayed spatial alternation was significantly impaired by MK-801 (0.1 mg/kg) at a longer delay, and ciproxifan (3.0 mg/kg) alleviated this impairment. These results indicate that some H3 antagonists can alleviate the impact of NMDA receptor hypofunction on some forms of memory, but may exacerbate its effect on other behaviors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats

et al. 2010

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“…However, these rats did not show any evidence of altered PPI or LI. An earlier study reported disrupted PPI in rats tested after nine daily injections with another NMDA receptor antagonist, dizocilpine, but that effect was context dependent and was seen in rats that received injections in the startle apparatus and not in the home cage (Schulz et al 2001). Our results, however, are consistent with those of Martinez et al (1999) who found normal PPI responses in rats receiving a variety of regimens of chronic or subchronic exposure to PCP.…”

Section: Discussionmentioning

confidence: 95%

Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition

2005

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“…1990; Swerdlow et al 1990;Braff et al 1992), as well as after administration of psychotomimetic agents such as d-amphetamine (Tenn et al 2003) and MK-801 (Schulz et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Olfactory learning prevents MK-801-induced psychosis-like behaviour in an animal model of schizophrenia

Naimark

Barkai

Michael

et al. 2008

The World Journal of Biological Psychiatry

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There is mounting evidence to support the concept that education is associated with the formation of a functional reserve in the brain, a process that appears to provide some protection against certain aspects of severe central nervous system disorders. The goal of this study was to examine whether learning prevents psychosis-like behaviour in an animal model of schizophrenia. A series of behavioural tasks were used to assess olfactory learning-induced protection against the effects of NMDA channel blocker, MK801. This blocker caused sensory-motor disturbances, spatial learning acquisition deficit, and swimming strategy alterations in pseudo-trained and naive rats, but had a considerably lesser effect on trained rats. In sharp contrast, olfactory learning provided no protection against d-amphetamine application. Our data support the notion that learning-induced protection against schizophrenic behaviour is maintained by non-NMDA-mediated enhanced activation of local connections in the relevant cortical networks.

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Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine

Abstract: Since PPI is considered as a measure of sensorimotor gating, our data indicate that sensorimotor gating deficits induced by MK-801 are subject to a sensitization process. These findings may be relevant for current hypotheses relating schizophrenic symptoms to sensitization.

Cited by 32 publications

References 1 publication

The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats

The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats

Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition

Olfactory learning prevents MK-801-induced psychosis-like behaviour in an animal model of schizophrenia

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