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Influence of aripiprazole, risperidone, and amisulpride on sensory and sensorimotor gating in healthy 'low and high gating' humans and relation to psychometry

Csomor, Philipp A. and Preller, Katrin H. and Geyer, Mark A. and Studerus, Erich and Huber, Theodor and Vollenweider, Franz X.. (2014) Influence of aripiprazole, risperidone, and amisulpride on sensory and sensorimotor gating in healthy 'low and high gating' humans and relation to psychometry. Neuropsychopharmacology, 39 (10). pp. 2485-2496.

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Official URL: https://edoc.unibas.ch/70611/

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Abstract

Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Bereich Psychiatrie (Klinik)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik)
03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK
03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Riecher-Rössler)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Riecher-Rössler)
UniBasel Contributors:Studerus, Erich
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:0893-133X
e-ISSN:1740-634X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:31 May 2020 09:33
Deposited On:31 May 2020 09:33

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