Ryabinin A E, Melia K R, Cole M, Bloom F E, Wilson M C
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
J Neurosci. 1995 Jan;15(1 Pt 2):721-30. doi: 10.1523/JNEUROSCI.15-01-00721.1995.
The ability of ethyl alcohol to modify responses to stress has been well documented (cf. Pohorecky, 1990). However, the structural substrate mediating these effects of alcohol remains undefined. Using immediate early gene (IEG) expression in the brain as a marker of altered neuronal response, we investigated the effect of acute alcohol exposure on the activity of brain regions of rats exposed to 15 min of restraint stress. Immunocytochemical localization c-Fos protein demonstrated that restraint stress led to an induction of c-Fos expression in several brain structures including cingulate and piriform cortex, cortico-amygdaloid and hippocampo-amygdaloid transition zones, hippocampus, hypothalamus, supramammillary nucleus, and centromedial nucleus of thalamus. An intraperitoneal injection of 2 g/kg alcohol prior to stress decreased c-Fos expression in several but not all of these structures. In particular, alcohol strongly attenuated the stress-induced expression of c-Fos in hippocampus and cingulate cortex. Using slot-blot hybridization, significant induction of c-fos mRNA after restraint stress was demonstrated both in hippocampus and cortex, but prior alcohol exposure specifically attenuated c-fos induction only in the hippocampus. The response of c-fos mRNA expression to stress and alcohol differed from the effects on jun-B, c-jun and jun-D mRNA levels. Perhaps surprisingly, acute exposure to alcohol in otherwise unstressed rats did not induce significant changes in expression of IEGs in comparison to control (saline-injected) animals even with doses sufficient to elevate plasma corticosterone. In summary, these studies demonstrate a selective sensitivity of stress-induced activity of neurons of hippocampus and cingulate cortex to acute alcohol exposure.
乙醇改变对应激反应的能力已有充分记载（参见Pohorecky，1990）。然而，介导酒精这些作用的结构底物仍不明确。我们以大脑中即刻早期基因（IEG）表达作为神经元反应改变的标志物，研究了急性酒精暴露对遭受15分钟束缚应激的大鼠脑区活性的影响。免疫细胞化学定位c-Fos蛋白表明，束缚应激导致包括扣带回和梨状皮质、皮质-杏仁核和海马-杏仁核过渡区、海马、下丘脑、乳头体上核以及丘脑中央内侧核在内的几个脑结构中c-Fos表达的诱导。在应激前腹腔注射2 g/kg酒精可降低其中几个但并非所有这些结构中的c-Fos表达。特别是，酒精强烈减弱了海马和扣带回皮质中应激诱导的c-Fos表达。使用狭缝印迹杂交法，证实束缚应激后海马和皮质中均有c-fos mRNA的显著诱导，但预先酒精暴露仅特异性减弱了海马中的c-fos诱导。c-fos mRNA表达对应激和酒精的反应不同于对jun-B、c-jun和jun-D mRNA水平的影响。也许令人惊讶的是，与对照（注射生理盐水）动物相比，在未受应激的大鼠中急性暴露于酒精，即使给予足以升高血浆皮质酮的剂量，也不会诱导IEG表达的显著变化。总之，这些研究表明海马和扣带回皮质神经元的应激诱导活性对急性酒精暴露具有选择性敏感性。
