Erdtmann-Vourliotis M, Mayer P, Riechert U, Höllt V
Institute for Pharmacology and Toxicology, Otto-von-Guericke Universität Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Brain Res Mol Brain Res. 1999 Aug 25;71(2):313-24. doi: 10.1016/s0169-328x(99)00207-7.
It is regarded as a common pharmacological property responsible for the addictive potential of drugs of abuse that they are able to activate brain areas involved in the sensation of pleasure, especially the nucleus accumbens. To investigate the connection between addictive potential and stimulation of critical brain areas in more detail, we studied c-fos accumulation in response to various addicting drugs in direct comparison. The substances were injected into drug-naive rats, and c-fos mRNA levels were measured throughout the brain by in situ hybridization. Cocaine in a high dose of 50 mg/kg yielded only a discrete c-fos expression in the medial and central striatum. Morphine (50 mg/kg) caused a weak c-fos synthesis in the lateral septum. THC (delta(9)-tetrahydrocannabinol), 25 mg/kg, induced c-fos mRNA again in the lateral septum and furthermore in large parts of the striatum including the nucleus accumbens. LSD (lysergic acid diamide), 1 mg/kg, elicited a similar c-fos expression pattern as THC, but there was additionally a very strong hybridization signal in the cerebral cortex, especially in the upper layers, and in the ventral part of the periaqueductal gray. The widest range of brain areas was activated by MDMA (3, 4-methylenedioxymethamphetamine, 'ecstasy'), 6 mg/kg. In addition to the regions that responded to LSD, there was a very pronounced c-fos signal in the nucleus accumbens core and shell and in the mammillary nuclei. Taken together, our study revealed that the drugs with the highest addictive potential, cocaine and morphine, yielded a very low c-fos synthesis throughout the brain whereas the brain regions closely linked to pleasure (especially the nucleus accumbens) responded strongly to drugs with an apparently lower addictive potential (THC, LSD, MDMA).
滥用药物具有成瘾潜力，其共同的药理学特性被认为是它们能够激活参与愉悦感的脑区，尤其是伏隔核。为了更详细地研究成瘾潜力与关键脑区刺激之间的联系，我们直接比较了各种成瘾药物作用下的c-fos积累情况。将这些物质注射到未接触过药物的大鼠体内，通过原位杂交测量全脑的c-fos mRNA水平。50mg/kg高剂量的可卡因仅在纹状体内侧和中央产生离散的c-fos表达。50mg/kg的吗啡在外侧隔区引起较弱的c-fos合成。25mg/kg的THC（δ9-四氢大麻酚）再次在外侧隔区以及包括伏隔核在内的纹状体大部分区域诱导c-fos mRNA表达。1mg/kg的LSD（麦角酸二乙酰胺）引发了与THC相似的c-fos表达模式，但在大脑皮层，尤其是上层，以及导水管周围灰质腹侧部分还存在非常强的杂交信号。6mg/kg的MDMA（3,4-亚甲基二氧甲基苯丙胺，“摇头丸”）激活的脑区范围最广。除了对LSD有反应的区域外，在伏隔核核心和壳以及乳头体核中有非常明显的c-fos信号。综上所述，我们的研究表明，成瘾潜力最高的药物可卡因和吗啡在全脑产生的c-fos合成非常低，而与愉悦感密切相关的脑区（尤其是伏隔核）对成瘾潜力明显较低的药物（THC、LSD、MDMA）反应强烈。
