Electron spin resonance spectroscopy reveals alpha-phenyl-N-tert-butylnitrone spin-traps free radicals in rat striatum and prevents haloperidol-induced vacuous chewing movements in the rat model of human tardive dyskinesia.

摘要: The typical antipsychotic drug haloperidol causes vacuous chewing movements (VCM) in rats, which are representative of early-Parkinsonian symptoms or later-onset extrapyramidal side effects tardive dyskinesia (TD) humans. Haloperidol (HP) has been hypothesized to potentiate increases oxidative stress free radical-mediated levels toxic metabolites rat striatum while simultaneous upregulating dopamine (DA)-D2 receptors leading presumed DA supersensitivity. Alpha(α)-Phenyl-N-tert-butylnitrone (PBN) is an antioxidant used combat and measure PBN spin-adduct activity. Thus, the aim this study was investigate whether VCMs related upregulation DA-D2 increased radicals produced during stress, had any protective effects. Rats received daily chronic (28 day) i.p. injections saline, (2 mg/kg), (150 + PBN. VCM model treatments. Electron spin resonance (ESR) spectroscopy performed compare concentrations radical species rats receiving HP To examine receptors, binding assays were carried out assess increase receptor numbers with respect following treatment injected HP, PBN, Results these experiments show that HP-induced results from cellular events may not be striatal receptors. Synapse 54:156–163, 2004. © 2004 Wiley-Liss, Inc.