Risperidone dose-dependently increases extracellular concentrations of serotonin in the rat frontal cortex: role of alpha 2-adrenoceptor antagonism

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
P HertelTorgny H Svensson

Abstract

We have previously shown that risperidone, an antipsychotic drug with high affinity for 5-hydroxytryptamine (5-HT)2A and dopamine (DA)2 receptors, as well as for alpha 2- and alpha 2-adrenoceptors, enhances 5-HT metabolism selectively in the rat frontal cortex (FC). To further study the influence of risperidone on central 5-HT systems, we compared its effects on dialysate 5-HT in the FC, as assessed by microdialysis, with those obtained with other antipsychotic drugs, i.e., clozapine, haloperidol, and amperozide, as well as with the selective alpha 2- or 5-HT2A receptor antagonists idazoxan or MDL 100,907, respectively. The underlying mechanism for risperidone's effect on 5-HT output in the FC was also investigated using single-cell recording in the dorsal raphe nucleus (DRN). Administration of risperidone (0.2, 0.6, and 2.0 mg/kg, SC) dose-dependently increased 5-HT levels in the FC. This stimulatory action was mimicked by amperozide (10 mg/kg, SC) and, to some extent, by idazoxan (0.25 mg/kg, SC). In contrast, clozapine (10 mg/kg, SC), haloperidol (2.0 mg/kg, SC), and MDL 100,907 (1.0 mg/kg, SC) exerted only minor effects on 5-HT output in brain. Local administration of risperidone or idazoxan (1.0-1000 mumol/L) in the FC dos...Continue Reading

Citations

Dec 4, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Torgny H Svensson
Apr 20, 2000·European Journal of Pharmacology·F J NasifO A Ramirez
Sep 23, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Patricia A BroderickYueping Zhou
Sep 2, 1998·Progress in Neuro-psychopharmacology & Biological Psychiatry·P HertelT H Svensson
Dec 15, 2000·Progress in Neurobiology·T M Tzschentke
Sep 7, 2000·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·K AntoniouZ Papadopoulou-Daifoti
Mar 21, 2001·Bipolar Disorders·S N GhaemiF K Goodwin
Jan 2, 2010·Behavioural Brain Research·Trisha A JenkinsStephen J Cooper
Aug 1, 2014·Behavioural Brain Research·Davide Amato
Oct 19, 2016·Pharmacological Reports : PR·Katarzyna KamińskaKrystyna Gołembiowska
Feb 17, 2018·Pharmaceutical Research·Willem Johan van den BrinkElizabeth Cunera Maria de Lange
Aug 11, 2004·CNS Spectrums·Olga Brawman-Mintzer, Kimberly A Yonkers

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