Locomotor activity and accumbens fos expression driven by ventral hippocampal stimulation require D1 and D2 receptors

Locomotor activity and accumbens fos expression driven by ventral hippocampal stimulation require D1 and D2 receptors
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DOI:
10.1016/s0306-4522(99)00303-6
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发表时间:
1999-01-01
期刊:
影响因子:
3.3
通讯作者:
Henry, JD
Henry, JD
中科院分区:
医学3区
文献类型:
--
作者:
Bardgett, ME;Henry, JD

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大量研究表明,大鼠腹侧海马到延髓核的兴奋性投射调节运动活动。此外,腹侧海马神经元改变自发活动的能力可能涉及在延髓核中发现的密集的多巴胺能神经支配。本研究的目的是:(i)更充分地表征腹侧海马活动急性改变的运动效应;(ii)确定多巴胺激动剂和拮抗剂对腹侧海马活动改变产生的运动变化的影响;(iii)使用立即早期基因诱导,以确定多巴胺拮抗剂是否改变腹侧海马刺激的背核神经元的反应。通过比较各种兴奋性氨基酸受体激动剂,发现腹侧海马输注N-甲基-D-天冬氨酸以亚惊厥方式升高运动活性,而其他兴奋性氨基酸受体激动剂则没有。通过利多卡因输注实现的腹侧海马失活不抑制正在进行的运动活动,也不影响安非他明诱导的运动活动增加。腹侧海马N-甲基-D-天冬氨酸输注诱导的自发活动增加可被氟哌啶醇(D-2受体拮抗剂)、SCH-23390(D-1受体拮抗剂)或利血平全身给药阻断。在腹侧海马N-甲基-D-天冬氨酸灌注后,立即早期基因c-fos蛋白产物的细胞表达显著增加,氟哌啶醇、SCH-23390和利血平减弱了这种作用。这些结果表明,腹侧海马活动的增加而不是减少对运动的持续速率有可测量的影响,这种作用需要D-1和D-2受体。此外,Fos表达的研究表明,多巴胺受体拮抗剂减弱神经元的反应腹侧海马刺激内的神经核,一个重要的大脑区域的产生和维持运动活动。(C)1999年IBRO。出版社:Elsevier Science Ltd
Numerous studies have suggested that excitatory projections from the ventral hippocampus to the nucleus accumbens modulate locomotor activity in rats. Furthermore, the ability of ventral hippocampal neurons to alter locomotor activity may involve the dense dopaminergic innervation found in the nucleus accumbens. The purpose of this study was to: (i) more fully characterize the locomotor effects of acute alterations in ventral hippocampal activity; (ii) ascertain the influence of dopamine agonists and antagonists on locomotor changes produced by altered ventral hippocampal activity; and (iii) use immediate early gene induction to determine whether dopamine antagonists alter the response of nucleus accumbens neurons to ventral hippocampal stimulation. By comparing a variety of excitatory amino acid agonists, it was found that ventral hippocampal infusion of N-methyl-D-aspartate elevated locomotor activity in a subconvulsive manner, while other excitatory amino acid receptor agonists did not. Inactivation of the ventral hippocampus achieved by lidocaine infusion did not suppress ongoing locomotor activity, nor did it affect amphetamine-induced increases in locomotor activity. Increases in locomotor activity induced by ventral hippocampal N-methyl-D-aspartate infusion were blocked by systemic administration of haloperidol (a D-2 receptor antagonist), SCH-23390 (a D-1 receptor antagonist) or reserpine. Cellular expression of the protein product of the immediate early gene, c-fos, was dramatically increased in the nucleus accumbens shell after ventral hippocampal N-methyl-D-aspartate infusion, and haloperidol, SCH-23390 and reserpine attenuated this effect.These results suggest that the increases, but not decreases, in ventral hippocampal activity have a measurable effect on ongoing rates of locomotion, and that this effect requires both D-1 and D-2 receptors. Moreover, the studies of Fos expression suggest that dopamine receptor antagonists attenuate neuronal responses to ventral hippocampal stimulation within the nucleus accumbens, a brain region important in the generation and maintenance of locomotor activity. (C) 1999 IBRO. Published by Elsevier Science Ltd.