Agmo A, Belzung C, Giordano M
Laboratoire de Psychophysiologie, Faculté des Sciences, Université de Tours, France.
J Neural Transm (Vienna). 1996;103(8-9):925-34. doi: 10.1007/BF01291783.
Ambulatory activity of male rats was quantified in an open field. The subjects were treated with DL-amphetamine and amfonelic acid alone or combined with the GABA transaminase inhibitors gamma-acetylen GABA (GAG) and sodium valproate as well as with the GABAA agonist THIP and the GABAB agonist baclofen. Subeffective doses of the GABAergic drugs did not modify the effects of moderate doses of the dopaminergic stimulants whereas effective doses continued to reduce ambulatory activity just as in the absence of dopaminergic activation. When DL-amphetamine or amfonelic acid were administered in doses that strongly enhanced ambulatory activity, doses of the GABAergic drugs that were inhibitory in the absence of dopaminergic stimulation were no longer effective. The mixed D1/D2 dopamine antagonist pimozide, the D1 antagonist SCH 23390 and the D2 antagonist sulpiride were then combined with subeffective doses of the GABA agonists. GAG, sodium valproate and baclofen were potentiated by pimozide and SCH 23390 but not by sulpiride. THIP was ineffective. These data show that GABAergic drugs had a reduced effect after stimulation of dopaminergic neurotransmission. On the other hand, when dopamine D1 receptors were blocked, nonselective GABA agonists and the GABAB agonist baclofen were potentiated. This was not the case for the GABAA agonist THIP, suggesting that the GABAA receptor is of slight importance for the interactions between GABA and dopamine in the control of ambulatory activity. No potentiation of GABAergic agonists was obtained after treatment with a dopamine D2 antagonist.
在旷场中对雄性大鼠的自主活动进行了量化。实验对象分别接受了DL-苯丙胺和安非尼酸单独给药，或与GABA转氨酶抑制剂γ-乙炔基GABA（GAG）和丙戊酸钠联合给药，以及与GABAA激动剂THIP和GABAB激动剂巴氯芬联合给药。GABA能药物的亚有效剂量并未改变中等剂量多巴胺能兴奋剂的作用，而有效剂量则继续降低自主活动，就如同不存在多巴胺能激活时一样。当以能强烈增强自主活动的剂量给予DL-苯丙胺或安非尼酸时，在不存在多巴胺能刺激时具有抑制作用的GABA能药物剂量不再有效。然后将混合的D1/D2多巴胺拮抗剂匹莫齐特、D1拮抗剂SCH 23390和D2拮抗剂舒必利与GABA激动剂的亚有效剂量联合使用。GAG、丙戊酸钠和巴氯芬被匹莫齐特和SCH 23390增强，但未被舒必利增强。THIP无效。这些数据表明，在多巴胺能神经传递受到刺激后，GABA能药物的作用减弱。另一方面，当多巴胺D1受体被阻断时，非选择性GABA激动剂和GABAB激动剂巴氯芬的作用增强。GABAA激动剂THIP并非如此，这表明GABAA受体在控制自主活动时GABA与多巴胺之间的相互作用中重要性较低。用多巴胺D2拮抗剂治疗后，未观察到GABA能激动剂的增强作用。
