0000000000113466
AUTHOR
Viola Fischer
Detection of TOAD-64 in adult rat brain as revealed by two-dimensional protein gel electrophoresis followed by MALDI mass spectrometry
The molecular mechanisms by which antipsychotic effects are achieved remain largely elusive. Possible mechanisms include the modulation of nerve cell gene expression. The antipsychotic drug haloperidol was administered orally (1.6 mg/kg) to adult rats for 3 weeks. Protein patterns in striata and forebrains were studied by two-dimensional gel electrophoresis (2-DE). One differentially regulated protein spot was identified by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) after trypsin digest. Turned on after devision-64 kD (TOAD-64), the identified protein, was present in all gels and, in addition, was up-regulated in the striata but not in the forebrains of the hal…
Distribution of clozapine and desmethylclozapine between blood and brain in rats.
Desmethylclozapine is the major metabolite of clozapine in serum. Although the metabolite is pharmacologically active in vitro, the occurrence of desmethylclozapine in brain under steady-state conditions and its role for clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5, 1, 2 and 5 h after the last administration, at a time four animals were killed for analysis of clozapine and desmethylclozapine concentrations in serum and brain. The treatment yielded steady-state serum concentrations of clozapine that are considered as therapeutically effective in man. Desmethylclozapine concentrat…
Induction of c-fos gene expression by the selective sigma receptor ligand EMD 57445 in rat brain.
Based on animal studies it has been reasoned that ligands to sigma binding sites might be effective in the treatment of schizophrenic disorders and may also be used to investigate this largely elusive disorder on a molecular level. Expression patterns of c-fos in rat brain were studied following treatment with single doses of the sigma ligand EMD 57445 (0.3, 1, 3, 30 mg/kg s.c.). Specific c-fos gene expression was detected at all concentrations tested in various cortical areas. The signals observed were dose-dependent with the highest intensities in the piriform cortex. Strong signals were also detected in hippocampal areas CA 1,2,3 and the gyrus dentatus, as well as in the medial habenula …
Chronic oral haloperidol and clozapine in rats: A behavioral evaluation.
The present study evaluated chronic oral treatment of rats with haloperidol or clozapine. Drugs were given in the drinking water for a 23-day period . Rat behavior was analyzed once a week in an open field. Rats ingested either 1.7 mg/kg haloperidol or 40 mg/kg clozapine daily. Blood serum analysis revealed concentrations of 6 ng/ml for haloperidol and 22 ng/ml for clozapine at the end of the treatment. Haloperidol decreased overall activity from the onset of treatment. Clozapine showed similar effects only on the last test day. Control animals showed a slight habituation in exploration-related parameters. In conclusion, these results indicate that oral drug administration through the drink…
Chronical haloperidol and clozapine treatment in rats: Differential RNA display analysis, behavioral studies and serum level determination
1. Adult, female rats were treated orally for 23 days with 1.6 mg/kg haloperidol or 36 mg/kg clozapine per day, to study chronic effects of the two neuroleptics. 2. At five time points during the neuroleptic treatment, animal behavior was recorded in an open field and locomotive activity was analysed. At the end of the experiment, rats were decapitated, blood samples were collected and serum concentrations of haloperidol and clozapine were determined by a radioreceptor or HPLC assay, respectively. RNA was isolated from each brain, without cerebellum, and subjected to differential RNA display. 3. Mean serum concentrations were 8 ng/ml for haloperidol and 21 ng/ml for clozapine. Analysis of o…