Abstract
Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of the startle response. M100907, a selective 5-HT2A-receptor antagonist that has been developed for clinical testing as an antipsychotic in schizophrenic patients, has been tested in several animal models of the gating deficits in schizophrenia, including PPI. Previous studies have shown that M100907 blocks or reduces the disruptive effects of hallucinogenic 5-HT2 agonists (e.g., DOI) and psychotomimetic NMDA antagonists (e.g., phencyclidine) on PPI. In the present paper, we report the results of three studies conducted to determine the effects of M100907 on apomorphine-induced disruption (one experiment) and isolation rearing-induced disruption of PPI in rats (two experiments). Results showed that M100907 failed to reduce the disruption of PPI caused by the dopamine agonist apomorphine. Nevertheless, M100907 partially reduced the disruption of PPI caused by isolation rearing. Thus, M100907 shows efficacy as a putative antipsychotic in nondopaminergic PPI models of the sensorimotor gating deficits in schizophrenia.
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Acknowledgements
This work was supported by grant R01-MH52885 from the National Institute of Mental Health (NIMH), by funding from the Department of Veteran Affairs through the VISN 22 MIRECC (Mental Illness, Research, Education and Clinical Center), and by an unrestricted educational grant from Hoechst Marion Roussel. Mark Geyer has an equity interest in San Diego Instruments, Inc. and was supported by Research Scientist Award K05-MH01228 from NIMH. The authors wish to thank Hoechst Marion Roussel for their generous gift of the M100907. We also thank Virginia Lehmann-Masten, Darlene Giracello, Barbara Carasso, and Arturo Solis for their excellent assistance throughout these studies.
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Geyer, M., Krebs-Thomson, K. & Varty, G. The Effects of M100907 in Pharmacological and Developmental Animal Models of Prepulse Inhibition Deficits in Schizophrenia. Neuropsychopharmacol 21 (Suppl 2), S134–S142 (1999). https://doi.org/10.1016/S0893-133X(99)00123-2
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DOI: https://doi.org/10.1016/S0893-133X(99)00123-2
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