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Titolo:
RISPERIDONE DOSE-DEPENDENTLY INCREASES EXTRACELLULAR CONCENTRATIONS OF SEROTONIN IN THE RAT FRONTAL-CORTEX - ROLE OF ALPHA(2)-ADRENOCEPTOR ANTAGONISM
Autore:
HERTEL P; NOMIKOS GG; SCHILSTROM B; ARBORELIUS L; SVENSSON TH;
Indirizzi:
KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL S-17177 STOCKHOLM SWEDEN KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL S-17177 STOCKHOLM SWEDEN
Titolo Testata:
Neuropsychopharmacology
fascicolo: 1, volume: 17, anno: 1997,
pagine: 44 - 55
SICI:
0893-133X(1997)17:1<44:RDIECO>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
D2-DOPAMINE RECEPTOR OCCUPANCY; ATYPICAL ANTIPSYCHOTIC-DRUGS; CHRONIC-SCHIZOPHRENIC PATIENTS; IN-VIVO DOPAMINE-D-2; DORSAL RAPHE; NUCLEUS-ACCUMBENS; BINDING PROPERTIES; PREFRONTAL CORTEX; NEGATIVE SYMPTOMS; DOUBLE-BLIND;
Keywords:
NEUROLEPTIC DRUGS; SEROTONIN; FRONTAL CORTEX; DORSAL RAPHE NUCLEUS; MICRODIALYSIS; ELECTROPHYSIOLOGY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
P. Hertel et al., "RISPERIDONE DOSE-DEPENDENTLY INCREASES EXTRACELLULAR CONCENTRATIONS OF SEROTONIN IN THE RAT FRONTAL-CORTEX - ROLE OF ALPHA(2)-ADRENOCEPTOR ANTAGONISM", Neuropsychopharmacology, 17(1), 1997, pp. 44-55

Abstract

We have previously shown that risperidone, an antipsychotic drug withhigh affinity for 5-hydroxytryptamine (5-HT)(2A) and dopamine (DA), receptors, as well as for alpha(1)- 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, toe compared its effects on dialysate 5-HT in the FC, Its 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 outputin the FC was also investigated using single-cell recording in the dorsal raphe nucleus (DRN). Administration of risperidone (0.2, 0.6, and2.0 mg/kg, SC) dose-dependently increased 5-HT levels in the FC. Thisstimulatory action was min-licked 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 mu mol/L) in the FC dose dependently increased dialysate levels of 5-HT in this region. On the other hand, risperidone 25-800 mu g/kg, IV) dose-dependently decreasedthe firing rate of 5-HT cells in the DRN, an effect that was largely antagonized by pretreatment with the selective 5-HT,, receptor antagonist WAY 100,635 (5.0 mu g/kg, IV). These results indicate that the risperidone-increased 5-HT output in the FC may be related to its alpha(2)-adrenoceptor antagonistic action, a property shared with both amperozide and idazoxan, and that this action probably is executed at the nerve terminal level. The inhibition of 5-HT cell firing by risperidone is probably secondary to increased 5-HT availability, e.g., in the DRN, since it could be antagonized by a 5-HT1A receptor antagonist. The enhanced 5-HT output in the FC by risperidone may be of particular relevance for the treatment of schizophrenia when associated with depression and in schizoaffective disorder. (C) 1997 American College of Neuropsychopharmacology.

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Documento generato il 01/10/20 alle ore 07:22:28