[3H]spiroperidol binding on lymphocytes : Changes in two different groups of schizophrenic patients and effect of neuroleptic treatment

Fur, G. Le; Zarifian, E.; Phan, T.; Cuché, H; Flamier, A.; F, Bouchami; Burgevin, Marie-Claude; Lôo, Henri; Gérard, Arlette; Uzan, A.

doi:10.1016/0024-3205(83)90037-1

Cited by 37 publications

(14 citation statements)

References 15 publications

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“…Wodarz et al LeFur et al (1980a) initially reported the presence of 3H-spiroperidol binding sites on rat and human peripheral lymphocytes as a model of a peripheral D2 dopamine receptor site. Consequently, in agreement with the dopamine hypothesis, a significant and selective increase in binding capacity (Bm~) for 3H-spiroperidol in lymphocytes of schizophrenic patients was described (LeFur et al 1983;Rotstein et al 1983;Bondy et al 1984;Ha[bach and Henning 1989;Grodzicki et al 1990). However, selection criteria of patients, methodological details and even Bm~ and Kd values of healthy subjects have differed widely between research groups.…”

Section: Introductionmentioning

confidence: 74%

3H-spiroperidol binding to human peripheral mononuclear cells: Methodological aspects

Wodarz

Fritze

Kornhuber

et al. 1992

Biological Psychiatry

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Section: Introductionmentioning

confidence: 74%

3H-spiroperidol binding to human peripheral mononuclear cells: Methodological aspects

Wodarz

Fritze

Kornhuber

et al. 1992

Biological Psychiatry

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“…In previous studies paranoid schizophrenics (LeFur et al 1983;Rotstein et al 1983) were reported to exhibit the highest Bmax values. In contrast, our schizophrenic patients with a paranoid subtype according to DSM-IlI-R-criteria did not show significantly different binding parameters compared to healthy individuals.…”

Section: Discussionmentioning

confidence: 82%

“…These authors proposed this binding as ape-ripheral model of the central D2-dopamine receptor site. Consequently, in line with the dopamine hypothesis, a significant and selective increase in binding capacity (Bm,~,) for 3H-spiroperidol in lymphocytes from schizophrenic patients was described (LeFur et al 1983;Rotstein et al 1983;Bondy et al 1984;Halbach and Henning 1989;Grodzicki et ai i990). Moreover, Bondy and Ackenheil (1987) reported a similar increase of Bma,, in healthy relatives of schizophrenics.…”

Section: Introductionmentioning

confidence: 78%

“…Initially, LeFur et al (1980bLeFur et al ( , 1983 reported an increase in 3H-spiroperidol binding sites on peripheral lymphocytes in schizophrenic patients and a decrease of these binding sites in idiopathic Parkinson's disease. Although some groups could confirm these findings in schizophrenics (Rotstein et al 1983;Bondy et al 1984;Halbach and Henning 1989;Grodzicki et al 1990) and patients with Parkinson's disease (Czlonkowska et al 1987;Bondy et al 1989), others were not able to replicate a binding site for 3H-spiroperidol in PBMC at all (Bloxham et al 1981;Fleminger et al 1982;Maloteaux et al 1982;Shaskan et al 1983;Feenstra et al 1989;Itzchaky et al 1989;Rao et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, selection criteria of schizophrenic patients differed between the groups. LeFur et al (1983) classified their patients in type I syndrome (acute schizophrenics with positive symptoms) and type II syndrome (chronic schizophrenics with negative symptoms). Bondy et al (1984) and Halbach and Henning (1989) classified their patients according to International Classification of Diseases (ICD) 9 criteria, but mentioned that only a minority of patients fulfilled DSM-III-R criteria of schizophrenia, as the majority of their patients suffered from their first and acute episode of illness.…”

Section: Discussionmentioning

confidence: 99%

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3H-spiroperidol binding to peripheral mononuclear cells in schizophrenic and healthy subjects

Wodarz

Fritze

Riederer

et al. 1993

Biological Psychiatry

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Dopamine receptors and the dopamine hypothesis of schizophrenia

Seeman

1987

Synapse

801

383

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The discovery of neuroleptic drugs in 1952 provided a new strategy for seeking a biological basis of schizophrenia. This entailed a search for a primary site of neuroleptic action. The Parkinsonian effects caused by neuroleptics suggested that dopamine transmission may be disrupted by these drugs. In 1963 it was proposed that neuroleptics blocked "monoamine receptors" or impeded the release of monoamine metabolites. The neuroleptic concentration in plasma water or cerebrospinal fluid was of the order of 2 nM for haloperidol in clinical therapy. A systematic research was made between 1963 and 1974 for a primary site of neuroleptic action which would be sensitive to 2 nM haloperidol and stereoselective for (+)-butaclamol. Direct evidence that neuroleptics selectively blocked dopamine receptors occurred in 1974 with the finding that nanomolar concentrations of these drugs stereoselectively inhibited the binding of [3H]-dopamine or [3H]-haloperidol. These binding sites, now termed D2 dopamine receptors (which inhibit adenylate cyclase), are blocked by neuroleptics in direct relation to the antipsychotic potencies of the neuroleptics. No such correlation exists for D1 receptors (which stimulate adenylate cyclase). Based on the fact that dopamine-mimetic drugs elicited hallucinations, and that neuroleptics caused rigidity, Van Rossum in 1966 had suggested a hypothesis that dopamine pathways may be overactive in schizophrenia. The D2-selective blockade by all neuroleptics (except the monoamine-depleting reserpine) provided strong support for the dopamine hypothesis. Further support now comes from postmortem data and in vivo positron tomographic data, both of which indicate that the density of D2 receptors are elevated in the schizophrenic brain. The postmortem data indicate a bimodal pattern with half the schizophrenics having striatal D2 densities of 14 pmol/g (control is 13 pmol/g) and the other half having 26 pmol/g. Current positron tomographic data indicate D2 densities of 14 pmol/g in control subjects, but values of 34 pmol/g in drug-naive schizophrenics. Future tests of the dopamine hypothesis of schizophrenia may entail an examination of the amino acid composition and genes for D2 receptors in schizophrenic tissue, an examination of the ability of the D2 receptor to become phosphorylated and to desensitize into the low-affinity state, and an examination of the interaction of D2 receptors with D1 receptors or other neurotransmitters.

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[3H]spiroperidol binding on lymphocytes : Changes in two different groups of schizophrenic patients and effect of neuroleptic treatment

Cited by 37 publications

References 15 publications

3H-spiroperidol binding to human peripheral mononuclear cells: Methodological aspects

3H-spiroperidol binding to human peripheral mononuclear cells: Methodological aspects

3H-spiroperidol binding to peripheral mononuclear cells in schizophrenic and healthy subjects

Dopamine receptors and the dopamine hypothesis of schizophrenia

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