Arango V, Ernsberger P, Sved A F, Mann J J
Laboratories of Neuropharmacology, Western Psychiatric Institute and Clinic University of Pittsburgh, PA 15213.
Brain Res. 1993 Dec 10;630(1-2):271-82. doi: 10.1016/0006-8993(93)90666-b.
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.
自杀受害者大脑中已发现血清素能和去甲肾上腺素能指标均有变化。为了更好地理解去甲肾上腺素能系统在自杀中的作用,我们分别使用[3H]哌唑嗪和[3H]-对氨基可乐定对α1-和α2-肾上腺素能受体进行了定量放射自显影。我们比较了自杀受害者和在死后延迟、年龄、脑侧和性别方面相匹配的对照组在前额叶皮质(PFC)中这些受体的分布和相对密度,以及颞叶皮质(TC)中α1-肾上腺素能受体的分布和相对密度。我们发现:(1)PFC(n = 20)和TC(n = 16)中α1-肾上腺素能受体的分层模式不同(P = 0.022);(2)与对照组相比,自杀受害者PFC的IV-V层对应的α1-肾上腺素能结合增加了37%(P = 0.029);(3)在所有皮质层中,TC的α1-肾上腺素能结合位点密度均高于PFC(P = 0.006);(4)α2-肾上腺素能结合位点在PFC(n = 24)中有特定的分层分布,在对照组和自杀受害者中并无差异;(5)自杀受害者PFC中与α2-肾上腺素能位点的结合与对照组无差异;(6)与对照组相比,自杀组相同脑区的去甲肾上腺素浓度升高,但与α1-或α2-肾上腺素能位点的结合无相关性。自杀受害者大脑中[3H]哌唑嗪(针对α1-肾上腺素能受体)结合增加,而[3H]-对氨基可乐定(针对α2-肾上腺素能受体)结合未增加,且去甲肾上腺素浓度升高,这为自杀与脑去甲肾上腺素能功能改变之间的关联提供了进一步证据。未来的研究必须确定脑去甲肾上腺素能功能的这些变化表明传递增加还是减少。