Quantitative autoradiography of alpha 1- and alpha 2-adrenergic receptors in the cerebral cortex of controls and suicide victims

Abstract

Alterations in both serotonergic and noradrenergic indices have been found in the brain of suicide victims. In order to better understand the role of the noradrenergic system in suicide, we carried out quantitative autoradiography of alpha 1- and alpha 2-adrenergic receptors using [3H]prazosin and [3H]-p-aminoclonidine respectively. We compared the distribution and relative density of these receptors in the prefrontal (PFC) and alpha 1-adrenergic receptors in the temporal cortex (TC) of suicide victims and controls matched for postmortem delay, age, side of brain and sex. We found that: (1) the laminar patterns of alpha 1-adrenergic receptors in the PFC (n = 20) and the TC (n = 16) were different (P = 0.022); (2) there was a 37% increase in alpha 1-adrenergic binding corresponding to layers IV-V of PFC of suicide victims compared to controls (P = 0.029); (3) the TC had a greater density of alpha 1-adrenergic binding sites than the PFC across all cortical layers (P = 0.006); (4) alpha 2-adrenergic binding sites had a specific laminar distribution in the PFC (n = 24) which did not differ in controls and suicide victims; (5) binding to alpha 2-adrenergic sites in the PFC of suicide victims did not differ from controls; and (6) norepinephrine concentrations in the same brain areas were elevated in the suicide group compared to controls, but did not correlate with binding to alpha 1- or alpha 2-adrenergic sites. The increase in [3H]prazosin (to alpha 1-adrenergic receptors) but not in [3H]-p-aminoclonidine (to alpha 2-adrenergic receptors), and in norepinephrine concentrations in the brain of suicide victims provides further evidence for an association between suicide and altered brain noradrenergic function. Future studies must determine whether these changes in brain noradrenergic function indicate increased or decreased transmission.