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Central D2 receptor blockade and antipsychotic effects of neuroleptics. Preliminary study with positron emission tomography

Published online by Cambridge University Press:  28 April 2020

JL Martinot ,
ML Paillère-Martinot ,
C Loc'h ,
P Péron Magnan ,
B Mazoyer ,
Y Lecrubier ,
P Hardy ,
B Beaufils ,
JF Allilaire  and
B Mazière
...Show all authors
JL Martinot*
Affiliation:
Service Hospitalier Frédéric-Joliot, CEA, Département de Biologie, 91406 Orsay Service de Psychiatrie (A Feline) Hôpital de Bicêtre, 94270, Le Kremlin Bicêtre
ML Paillère-Martinot
Affiliation:
Service de Psychopathologie de l'enfant et de l'adolescent (M Basquin) Hôpital de La Salpétrière, 75013, Paris
C Loc'h
Affiliation:
Service Hospitalier Frédéric-Joliot, CEA, Département de Biologie, 91406 Orsay
P Péron Magnan
Affiliation:
Service Hospitalier Universitaire (H Loo) Hôpital Sainte-Anne, 75014, Paris
B Mazoyer
Affiliation:
Service Hospitalier Frédéric-Joliot, CEA, Département de Biologie, 91406 Orsay
Y Lecrubier
Affiliation:
INSERM U302, Psychopharmacologie et psychopathologie des comportements. Hôpital de La Salpêtrière, 75013, Paris
P Hardy
Affiliation:
Service de Psychiatrie (A Feline) Hôpital de Bicêtre, 94270, Le Kremlin Bicêtre
B Beaufils
Affiliation:
Service de Psychiatrie (A Feline) Hôpital de Bicêtre, 94270, Le Kremlin Bicêtre
JF Allilaire
Affiliation:
Service de Psychiatrie (D Widlocher) Hôpital de La Salpêtrière, 75013, Paris
B Mazière
Affiliation:
Service Hospitalier Frédéric-Joliot, CEA, Département de Biologie, 91406 Orsay
MF Slama
Affiliation:
Service de Psychiatrie (D Ginestet) Hôpital Paul-Brousse, 94800, Villejuif, France
A Syrota
Affiliation:
Service Hospitalier Frédéric-Joliot, CEA, Département de Biologie, 91406 Orsay
*
*Correspondence and reprints. Service de Psychiatrie, Hôpital de Bicêtre, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France
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Summary

The striatal D2 receptor density/affinity index was assessed using positron emission tomography and 76Br-Bromolisuride in 15 schizophrenics, first untreated, and afterwards receiving neuroleptics, and in 14 control subjects. The patients received low or conventional doses of neuroleptics. The schizophrenics receiving low doses (n = 6) had preponderant negative symptoms. Mean D2 receptor occupancy was 24 ± 20%. Despite this weak central D2 receptor blockade, a significant decrease in negative symptoms was observed, a result consistent with the hypothesis of a disinhibitory action of some neuroleptics administered in low doses. The patients treated with conventional doses (n = 9) had mixed positive and negative symptoms, and the mean D2 receptor occupancy was 54 ± 13%. Significant decreases in positive symptoms, but also in negative symptoms, were obtained with this treatment. Before treatment, there was no significant difference in the striatal D2 receptor density/affinity index between: 1) patients and controls, 2) negative and mixed schizophrenics, and 3) the subsequent responder and non-responder patients. In addition, the D2 dopamine receptor occupancy by neuroleptics did not significantly differ in responder or nonresponder patients, suggesting that the central D2 dopamine receptor blockade is a necessary, but insufficient condition to account for the antipsychotic effect of neuroleptics.

Résumé

Résumé

La densité des récepteurs dopaminergiques D2 striataux a été estimée chez 15 schizophrènes d'abord non traités puis au cours d'un traitement neuroleptique, et chez 14 témoins, en utilisant la tomographie par émission de positons et le 76Br-Bromolisuride. Les patients ont reçu des doses faibles, «désinhibitrices» ou des doses classiques de neuroleptiques. Les schizophrènes ayant reçu de faibles doses avaient une symptomatologie négative prépondérante. Le pourcentage moyen d'occupation des récepteurs D2 était de 24 ± 20%. Malgré ce faible blocage des récepteurs D2, une réduction significative des symptômes négatifs a été observée, un résultat compatible avec l'hypothèse d'un effet désinhibiteur des faibles doses de certains neuroleptiques. Les patients traités par doses classiques avaient une symptomatologie mixte, et le pourcentage d'occupation des récepteurs était de 54 ± 13%. Ce traitement a apporté une réduction significative des symptômes positifs mais aussi négatifs. Avant traitement, l'estimation de la densité des récepteurs D2 striataux ne différait pas entre: 1) les patients et les témoins; 2) les schizophrènes négatifs et les schizophrènes mixtes; et 3) les patients ultérieurement répondeurs ou non répondeurs au traitement. Chez les patients traités, les pourcentages d'occupation des récepteurs D2 des patients répondeurs n'étaient pas significativement différents de ceux des non-répondeurs, suggérant que l'occupation des récepteurs D2 est une condition nécessaire mais sans doute insuffisante pour rendre compte de l'effet antipsychotique des neuroleptiques.

Keywords

schizophreniapositron emission tomographyD2 dopamine receptorsneurolepticsschizophrénietomographie d'émission de positonsrécepteurs dopaminergiques D2neuroleptiques
Type
Original article
Information
Psychiatry and Psychobiology , Volume 5 , Issue 4 , 1990 , pp. 231 - 240
Copyright
Copyright © European Psychiatric Association 1990

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