Dopaminergic agonists administered into the nucleus accumbens: Effects on extracellular glutamate and on locomotor activity
Dopaminergic agonists administered into the nucleus accumbens: Effects on extracellular glutamate and on locomotor activity
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DOI：
10.1016/s0006-8993(97)01518-7
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发表时间：
1998-03-30
期刊：
影响因子：
2.9
通讯作者：
Wallace, LJ
中科院分区：
文献类型：
--
作者：
Dalia, A;Uretsky, NJ;Wallace, LJ
有待检验的假设是，安非他明在伏隔核诱导的多巴胺能传递增加，导致该脑区谷氨酸能神经传递增加，该神经递质水平的增加有助于精神刺激性药物的行为效应。苯丙胺(1 mg/kg，ip)通过体内透析测定，增加伏隔核细胞外谷氨酸的含量，并刺激运动活动。通过探头通过反向透析将苯丙胺(10 MM)注入伏隔核，可产生与全身安非他明相似的运动活动刺激，但细胞外谷氨酸水平的增加更大。选择性的D1拮抗剂SCH23390或选择性的D2拮抗剂乙氯必利均可减弱苯丙胺的上述反应。通过反向透析将D1和D2激动剂SKF38393(20 MM)和奎比罗(50 MM)联合注入伏隔核，也可增加细胞外谷氨酸并刺激运动活动。给予谷氨酸摄取抑制剂苏β-羟基-天冬氨酸(50 MM)可增加细胞外谷氨酸，但不能刺激运动活动。全身注射咖啡因(15 mg/kg，i.p.)增加运动活性，但不增加细胞外谷氨酸水平。这些数据表明，伏隔核多巴胺能受体的激活导致该脑区运动活动的刺激和谷氨酸能传递的激活。然而，伏隔核中谷氨酸水平的增加既不足以也不必要产生运动活动的刺激。(C)1998年爱思唯尔科学公司。
The hypothesis to be tested was that increased dopaminergic transmission induced by amphetamine in the nucleus accumbens results in increased glutamatergic neurotransmission in this brain area and that the increase in level of this neurotransmitter contributes to behavioral effects of psychostimulant drugs. Amphetamine (1 mg/kg, i.p.) increased the amount of extracellular glutamate in the accumbens, as measured by in vivo dialysis, and stimulated locomotor activity. Amphetamine (10 mM) infused into the accumbens by reverse dialysis through the probe produced a similar stimulation of locomotor activity as systemic amphetamine but a greater increase in extracellular glutamate levels. Both of these responses to amphetamine were attenuated by either the selective D1 antagonist SCH23390 or the selective D2 antagonist eticlopride. The combination of a D1 and D2 agonist, SKF38393 (20 mM) and quinpirole (50 mM), administered into the accumbens by reverse dialysis also increased extracellular glutamate and stimulated locomotor activity. Administration of a glutamate uptake inhibitor, threo-beta-hydroxy-aspartate (50 mM), increased extracellular glutamate but did not stimulate locomotor activity. Systemic administration of caffeine (15 mg/kg, i.p.) increased locomotor activity but did not increase extracellular levels of glutamate. These data suggest that activation of dopaminergic receptors in the nucleus accumbens results in stimulation of locomotor activity and in activation of glutamatergic transmission in this brain region. However, an increase in glutamate levels in the nucleus accumbens is neither sufficient nor necessary to produce a stimulation of locomotor activity. (C) 1998 Elsevier Science B.V.