Serotonin 1a receptor and associated G-protein activation in schizophrenia and bipolar disorder

Gray, Laura; Scarr, Elizabeth; Dean, Brian

doi:10.1016/j.psychres.2005.09.010

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Volume 143, Issue 2 , Pages 111-120, 30 August 2006

Serotonin 1a receptor and associated G-protein activation in schizophrenia and bipolar disorder

Laura Gray
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia
- Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
Elizabeth Scarr
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia
- Centre for Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia
Brian Dean
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia
- Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
- Department of Psychiatry, The University of Melbourne, Parkville, Victoria 3010, Australia
- Department of Psychological Medicine, Monash University, Clayton, Victoria 3800, Australia
- Corresponding author. The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia. Tel.: +61 3 9389 3940; fax: +61 3 9387 5061.

Received 31 May 2005; received in revised form 22 August 2005; accepted 16 September 2005.

Abstract

Abnormalities in the serotonergic signalling system, including the serotonin 1a receptor, have been implicated in the pathogenesis of schizophrenia and bipolar 1 disorder. However, there is no consensus on whether the density of the serotonin 1a receptor and/or the activity of the G-proteins linking the receptor to the intracellular cascade are altered in these disease states. To address these issues, tissue obtained postmortem from four cortical regions was used to measure [³H] 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) binding and 8-OH-DPAT-stimulated guanosine 5′-[γ-thio]triphosphate (GTPγS) binding to determine if either parameter is altered in schizophrenia or bipolar I disorder. There was an effect of diagnosis on the level of [³H] 8-OH-DPAT binding that may indicate a global change in the density of serotonin 1a receptors, although this effect did not reach significance in any individual brain region. The activation of serotonin 1a receptors did not differ significantly with diagnoses. However, in the outer cortical layers, there appeared to be a dissociation between the number of receptors available and the extent of ligand-induced GTPγS binding, suggesting considerable receptor reserve. In addition, comparing gender independent of diagnoses, a decrease in the levels of serotonin 1a receptors was observed in the cortex of female subjects. These data indicates that there may be subtle changes in serotonin 1a receptors across the cortex in schizophrenia or bipolar I disorder and suggests a gender discordance in receptor levels.

Keywords: 8-OH-DPAT, Cortex, Gender, GTPγS, Psychosis