Reduced serotonin 5-HT1A receptor binding in the temporal cortex correlates with aggressive behavior in Alzheimer disease.
Previous studies have implicated brain serotonin 5-HT(1A) receptors in several CNS functions, including cognition, mood and emotional states. In Alzheimer disease (AD), cognitive impairment and behavioral symptoms are the main clinical features. However, the biochemical basis of such changes is poorly understood. Results from recent in vivo studies suggest that 5-HT(1A) receptors may be related to aggressive traits in healthy subjects. The present study investigated the state of 5-HT(1A) receptors in the postmortem neocortex of 33 AD patients prospectively assessed for cognition and behavioral symptoms, together with 20 matched controls, by saturation [(3)H]8-OH-DPAT binding assays. 5-HT(1A) receptor binding affinity (K(D)) and density (B(max)) were unchanged in the overall AD group compared with controls. Within the AD group, 5-HT(1A) receptor B(max) in the temporal cortex inversely correlated with aggression and dementia severity. However, multiple regression analyses showed that 5-HT(1A) receptor B(max) remained the best predictor for aggression, while temporal cortical neurofibrillary tangle grading was the best predictor for dementia severity. This suggests that 5-HT(1A) receptor alteration is directly related to aggression in AD, while dementia severity is more strongly related to the neurodegenerative process. Our data indicate further study of 5-HT(1A) receptors as a pharmacological target for the treatment of behavioral symptoms in AD.
Department of Clinical Research, Singapore General Hospital, Singapore. admin@dementia-research.org
Mitchell K P
MK
Lai
Shirley W Y
SW
Tsang
Paul T
PT
Francis
Margaret M
MM
Esiri
Janet
J
Keene
Tony
T
Hope
Christopher P L-H
CP
Chen
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000523:psychology*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008297:Male; D008566:Membranes / Q000378:metabolism; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013702:Temporal Lobe / Q000378:metabolism*
D008024:Ligands; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin