Söderpalm A, Ehrenström F, Söderpalm B
Institute of Physiology and Pharmacology, Göteborg University, Sweden.
J Neural Transm Gen Sect. 1995;100(3):191-206. doi: 10.1007/BF01276458.
In a companion paper the alpha 2-adrenoceptor antagonist yohimbine was found to produce a dose-dependent anticonflict effect in a modified Vogel's conflict test. The behavioral data further indicated that noradrenergic and serotonergic neurons as well as the benzodiazepine (BDZ) receptor may be involved in the anticonflict effect of yohimbine. In the present study the effects on rat brain monoamine neurochemistry and GABAA/BDZ receptor function (36Cl-uptake in corticohippocampal synaptoneurosomes) of a maximally anticonflict producing dose of yohimbine (4.0 mg/kg, i.p.) were studied. The levels of rat brain catecholamines and indoleamines were measured ex vivo using high performance liquid chromatography with electrochemical detection (HPLC-ED). Yohimbine decreased noradrenaline levels both in the hippocampus and the hemispheres but instead increased DOPAC levels in these brain regions as well as in the limbic forebrain. Yohimbine also markedly enhanced DOPA accumulation in the hippocampus and the hemispheres after inhibition of 1-aromatic amino acid decarboxylase by means of NSD 1015, whereas in the limbic system only a modest increase was obtained. The yohimbine-induced effects on the catecholamine synthesis rate were largely abolished in animals severely depleted of NA by means of 6-hydroxy-dopamine (6-OH-DA) pretreatment. Yohimbine decreased both the 5-HIAA/5-HT quotient (an indicator of 5-HT turnover) and 5-HTP accumulation after NSD 1015 in the hemispheres, whereas in the hippocampus and the limbic system only 5-HTP accumulation was decreased. The yohimbine-induced effect on the indoleamine synthesis rate was not influenced by 6-OH-DA pretreatment, whereas this effect and that on the catecholamine synthesis rate were both abolished by reserpine pretreatment. Neither in vivo nor in vitro administration of yohimbine significantly altered baseline or GABA-induced accumulation of 36Cl- in corticohippocampal synaptoneurosomes. In conclusion, the present study provides neurochemical support for the suggestion that yohimbine may exert its anticonflict effect in a modified Vogel's conflict test by increasing and decreasing NA and 5-HT neurotransmission, respectively, whereas no evidence was obtained for a direct interaction of yohimbine with GABAA/BDZ receptor function.
在一篇相关论文中，发现α2-肾上腺素能受体拮抗剂育亨宾在改良的Vogel冲突试验中产生剂量依赖性的抗冲突效应。行为学数据进一步表明，去甲肾上腺素能和5-羟色胺能神经元以及苯二氮䓬（BDZ）受体可能参与了育亨宾的抗冲突效应。在本研究中，研究了产生最大抗冲突效应剂量的育亨宾（4.0mg/kg，腹腔注射）对大鼠脑单胺神经化学和GABAA/BDZ受体功能（皮质海马突触体中的36Cl摄取）的影响。使用高效液相色谱-电化学检测法（HPLC-ED）离体测量大鼠脑儿茶酚胺和吲哚胺的水平。育亨宾降低了海马体和大脑半球中的去甲肾上腺素水平，但却增加了这些脑区以及边缘前脑中的二羟基苯乙酸（DOPAC）水平。在通过NSD 1015抑制芳香族氨基酸脱羧酶后，育亨宾还显著增强了海马体和大脑半球中的多巴积累，而在边缘系统中仅获得了适度的增加。通过6-羟基多巴胺（6-OH-DA）预处理使去甲肾上腺素严重耗竭的动物中，育亨宾对儿茶酚胺合成速率的诱导作用在很大程度上被消除。育亨宾降低了大脑半球中5-羟吲哚乙酸/5-羟色胺（5-HIAA/5-HT）比值（5-HT周转的指标）以及NSD 1015处理后的5-羟色胺酸（5-HTP）积累，而在海马体和边缘系统中仅5-HTP积累减少。育亨宾对吲哚胺合成速率的诱导作用不受6-OH-DA预处理的影响，而这种作用以及对儿茶酚胺合成速率的作用均被利血平预处理消除。无论是体内还是体外给予育亨宾，均未显著改变皮质海马突触体中36Cl的基线或GABA诱导的积累。总之，本研究为以下观点提供了神经化学支持：育亨宾在改良的Vogel冲突试验中可能分别通过增加和减少去甲肾上腺素能和5-羟色胺能神经传递来发挥其抗冲突效应，而未获得育亨宾与GABAA/BDZ受体功能直接相互作用的证据。
