Ojanen Sami P, Palmén Maria, Hyytiä Petri, Kiianmaa Kalervo
Department of Mental Health and Alcohol Research, National Public Health Institute, POB 33, 00251 Helsinki, Finland.
Eur J Pharmacol. 2007 Mar 15;559(1):38-45. doi: 10.1016/j.ejphar.2006.11.046. Epub 2006 Dec 2.
Glutamate and gamma-amino-butyric acid (GABA) have been implicated in neuronal plasticity related to behavioral sensitization. In the present study, we examined morphine-induced changes in the extracellular concentrations of glutamate and GABA in the ventral tegmental area in alcohol-preferring Alko Alcohol (AA) and alcohol-avoiding Alko Non-Alcohol (ANA) rats that have previously been shown to differ in morphine-induced sensitization. The rats were given escalating doses (5-20 mg/kg) of morphine every other day for five days. This treatment produced behavioral sensitization to locomotor effects of morphine in AA, but not in ANA rats, when challenged with an additional injection of morphine (10 mg/kg) 10 days later. Morphine also increased the levels of glutamate in the ventral tegmental area only in AA rats, while no significant changes were found in the extracellular concentrations of GABA between the lines. Challenging the morphine-treated AA rats with ethanol (1.5 g/kg) did not modify the levels of glutamate or GABA. No changes in the concentrations of glutamate or GABA were seen in saline-treated AA and ANA rats after morphine challenge. These results render increased glutamate transmission in the ventral tegmental area a potential contributor to the higher susceptibility of AA rats to morphine-induced behavioral and neurochemical effects relative to ANA rats.
谷氨酸和γ-氨基丁酸（GABA）与行为敏化相关的神经元可塑性有关。在本研究中，我们检测了吗啡诱导的酒精偏好型Alko酒精（AA）大鼠和酒精回避型Alko非酒精（ANA）大鼠腹侧被盖区谷氨酸和GABA细胞外浓度的变化，此前已表明这两种大鼠在吗啡诱导的敏化方面存在差异。每隔一天给大鼠注射递增剂量（5 - 20 mg/kg）的吗啡，持续五天。10天后额外注射吗啡（10 mg/kg）进行激发试验时，这种处理使AA大鼠对吗啡的运动效应产生行为敏化，但ANA大鼠未出现。吗啡还仅在AA大鼠中增加了腹侧被盖区谷氨酸的水平，而两品系之间GABA的细胞外浓度未发现显著变化。用乙醇（1.5 g/kg）激发经吗啡处理的AA大鼠并未改变谷氨酸或GABA的水平。在吗啡激发试验后，生理盐水处理的AA和ANA大鼠中谷氨酸或GABA的浓度未见变化。这些结果表明，腹侧被盖区谷氨酸传递增加可能是AA大鼠相对于ANA大鼠对吗啡诱导的行为和神经化学效应更敏感的一个潜在因素。
