Enhanced Cortical Dopamine Output and Antipsychotic-like Effects of Raclopride by α 2 Adrenoceptor Blockade
- 1 October 1999
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 286 (5437) , 105-107
- https://doi.org/10.1126/science.286.5437.105
Abstract
Clozapine exerts superior clinical efficacy and markedly enhances cortical dopamine output compared with classical antipsychotic drugs. Here the α 2 adrenoceptor antagonist idazoxan was administered to rats alone or in combination with the D 2/3 dopamine receptor antagonist raclopride. Dopamine efflux in the medial prefrontal cortex and conditioned avoidance responding were analyzed. Idazoxan selectively potentiated the cortical output of dopamine and augmented the suppression of conditioned avoidance responding induced by raclopride. These results challenge basic assumptions underlying the dopamine hypothesis of schizophrenia and provide insight into clozapine's mode of action.Keywords
This publication has 49 references indexed in Scilit:
- Idazoxan and Response to Typical Neuroleptics in Treatment-Resistant SchizophreniaThe British Journal of Psychiatry, 1996
- Chronic clozapine selectively decreases prefrontal cortex dopamine as shown by simultaneous cortical, accumbens, and striatal microdialysis in freely moving ratsPharmacology Biochemistry and Behavior, 1995
- Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophreniaNature, 1995
- Putting the 'A' in atypical: does α2-adrenoceptor antagonism account for the therapeutic advantage of new antipsychotics?Journal of Psychopharmacology, 1994
- Treatment of schizophrenia: A clinical and preclinical evaluation of neuroleptic drugsPharmacology & Therapeutics, 1993
- Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsyJournal Of Neural Transmission-Parkinsons Disease and Dementia Section, 1991
- Acute Effects of Typical and Atypical Antipsychotic Drugs on the Release of Dopamine from Prefrontal Cortex, Nucleus Accumbens, and Striatum of the Rat: An In Vivo Microdialysis StudyJournal of Neurochemistry, 1990
- Pharmacological Specificity of Conditioned Avoidance Response Inhibition in Rats: Inhibition by Neuroleptics and Correlation to Dopamine Receptor BlockadeActa Pharmacologica et Toxicologica, 1982
- Correlation between antiavoidance activities of antipsychotic drugs in rats and daily clinical dosesPharmacology Biochemistry and Behavior, 1981
- Cognitive Deficit Caused by Regional Depletion of Dopamine in Prefrontal Cortex of Rhesus MonkeyScience, 1979