5‐HT 6 receptor binding sites in schizophrenia and following antipsychotic drug administration: Autoradiographic studies with [ 125 I]SB‐258585
Abstract The 5‐hydroxytryptamine (5‐HT; serotonin)‐6 receptor (5‐HT 6 R) is a putative target of atypical antipsychotic drugs and its mRNA expression is altered in schizophrenia. [ 125 I]SB‐258585 is a selective 5‐HT 6 R antagonist which has been well characterized for use in the rat brain. The pres...
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| Published in | Synapse (New York, N.Y.) Vol. 45; no. 3; pp. 191 - 199 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
01.09.2002
|
| Online Access | Get full text |
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| Abstract | Abstract
The 5‐hydroxytryptamine (5‐HT; serotonin)‐6 receptor (5‐HT
6
R) is a putative target of atypical antipsychotic drugs and its mRNA expression is altered in schizophrenia. [
125
I]SB‐258585 is a selective 5‐HT
6
R antagonist which has been well characterized for use in the rat brain. The present study evaluated its suitability for receptor autoradiography in the human brain and its application to quantitative studies. The affinity (K
d
∼1.2 nM) and relative distribution of binding sites (striatum ≫ cortex ∼ hippocampus) were similar to the rat. The distribution of [
125
I]SB‐258585 binding in these regions was also consistent with that of 5‐HT
6
R mRNA, determined in parallel using in situ hybridization. [
125
I]SB‐258585 binding site densities were measured in dorsolateral prefrontal cortex of 20 patients with chronic schizophrenia and compared with 17 normal subjects. No differences were seen between groups. Neither were [
125
I]SB‐258585 binding site densities affected in the frontal cortex or striatum of rats following 2 weeks' administration of the antipsychotic drugs haloperidol, chlorpromazine, olanzapine, risperidone, or clozapine. In summary, [
125
I]SB‐258585 is a suitable radioligand for studies of human brain 5‐HT
6
R binding sites and shows that their distribution is broadly similar to that of the rodent. The lack of effect of schizophrenia or antipsychotic drug administration on [
125
I]SB‐258585 binding suggests that an altered receptor density does not contribute to any involvement which the 5‐HT
6
R may have in the disease or its treatment. Synapse 45:191–199, 2002. © 2002 Wiley‐Liss, Inc. |
|---|---|
| AbstractList | Abstract
The 5‐hydroxytryptamine (5‐HT; serotonin)‐6 receptor (5‐HT
6
R) is a putative target of atypical antipsychotic drugs and its mRNA expression is altered in schizophrenia. [
125
I]SB‐258585 is a selective 5‐HT
6
R antagonist which has been well characterized for use in the rat brain. The present study evaluated its suitability for receptor autoradiography in the human brain and its application to quantitative studies. The affinity (K
d
∼1.2 nM) and relative distribution of binding sites (striatum ≫ cortex ∼ hippocampus) were similar to the rat. The distribution of [
125
I]SB‐258585 binding in these regions was also consistent with that of 5‐HT
6
R mRNA, determined in parallel using in situ hybridization. [
125
I]SB‐258585 binding site densities were measured in dorsolateral prefrontal cortex of 20 patients with chronic schizophrenia and compared with 17 normal subjects. No differences were seen between groups. Neither were [
125
I]SB‐258585 binding site densities affected in the frontal cortex or striatum of rats following 2 weeks' administration of the antipsychotic drugs haloperidol, chlorpromazine, olanzapine, risperidone, or clozapine. In summary, [
125
I]SB‐258585 is a suitable radioligand for studies of human brain 5‐HT
6
R binding sites and shows that their distribution is broadly similar to that of the rodent. The lack of effect of schizophrenia or antipsychotic drug administration on [
125
I]SB‐258585 binding suggests that an altered receptor density does not contribute to any involvement which the 5‐HT
6
R may have in the disease or its treatment. Synapse 45:191–199, 2002. © 2002 Wiley‐Liss, Inc. |
| Author | East, Simon Z. Burnet, Philip W.J. Leslie, Ronald A. Harrison, Paul J. Roberts, Jennifer C. |
| Author_xml | – sequence: 1 givenname: Simon Z. surname: East fullname: East, Simon Z. – sequence: 2 givenname: Philip W.J. surname: Burnet fullname: Burnet, Philip W.J. – sequence: 3 givenname: Ronald A. surname: Leslie fullname: Leslie, Ronald A. – sequence: 4 givenname: Jennifer C. surname: Roberts fullname: Roberts, Jennifer C. – sequence: 5 givenname: Paul J. surname: Harrison fullname: Harrison, Paul J. |
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The 5‐hydroxytryptamine (5‐HT; serotonin)‐6 receptor (5‐HT
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