Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides

Abstract

Serotonergic dysfunction is present in mood disorders and suicide. Brainstem 5-HT 1A somatodendritic autoreceptors regulate serotonin neuron firing but studies of autoreceptor binding in the dorsal raphe nucleus (DRN) in depressed suicides report conflicting results. We sought to determine: (1) the anatomical distribution of 5-HT 1A receptor binding in the DRN in depressed suicides and psychiatrically normal controls; and (2) whether sex differences in 5-HT 1A binding in the DRN contribute to differences between depressed suicides and controls. Previously collected quantitative receptor autoradiograms of [ 3H]8-hydroxy-2-(di- n-propyl)aminotetralin ( 3H-8-OH-DPAT) in postmortem tissue sections containing the DRN from drug-free suicide victims ( n = 10) and matched controls ( n = 10) were analyzed. Less total receptor binding (fmol/mg tissue × mm 3) was observed in the entire DRN in depressed suicides compared with controls ( p < 0.05). Group differences along the rostrocaudal extent of the DRN were observed for cross-sectional 5-HT 1A binding (fmol/mg tissue) and receptor binding (fmol/mg × mm 3, p < 0.05). Cross-sectional 5-HT 1A DRN binding in depressed suicides compared with controls was higher rostrally and lower caudally. The differences between depressed suicides and controls were present in males and females, although females had more binding than males. Less autoreceptor binding in the DRN of depressed suicides may represent a homeostatic response to less serotonin release, increasing serotonin neuron firing. More autoreceptor binding in rostral DRN might contribute to deficient serotonin release in ventromedial prefrontal cortex by lower neuronal firing.