Tuinstra T, Cools A R
Department of Psychoneuropharmacology, University of Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Neuroscience. 2000;99(1):55-64. doi: 10.1016/s0306-4522(00)00139-1.
The main goal of this study was to provide in vivo neurochemical evidence that mesolimbic alpha- and beta-adrenoceptors direct the release of mesolimbic dopamine. Both high responders to novelty and low responders to novelty were used to study the effects of intra-accumbal administered adrenergic agents on the dopamine release in the nucleus accumbens during two conditions, namely at rest (non-challenge) and when exposed to a "new cage" (challenge). Under non-challenged condition: phenylephrine (alpha-adrenergic agonist) induced a dose-dependent increase in dopamine release that was significantly larger in high responders; phentolamine (alpha-adrenoceptor antagonist) also induced a dose-dependent increase in dopamine that was significantly larger in low responders; isoproterenol (beta-adrenoceptor agonist) induced a dose-dependent increase in dopamine that did not differ between the two types of rat; propranolol (beta-adrenoceptor antagonist) did not change the dopamine release. Under challenged condition: phenylephrine and phentolamine both increased dopamine release without type-specific differences; only in low responders did isoproterenol increase the novelty-induced dopamine release; only in high responders did propranolol decrease the novelty-induced dopamine release. The in vivo neurochemical data are discussed in view of the outcome of earlier reported in vitro studies and pharmaco-behavioral studies. Overall the data reveal that mesolimbic noradrenaline has a dual role in the nucleus accumbens. It is argued that stimulation of alpha-adrenoceptors and beta-adrenoceptors, located postsynaptically on dopamine nerve-endings, inhibits and facilitates, respectively, dopamine release, whereas stimulation of presynaptic alpha-adrenoceptors inhibits the release of noradrenaline and, subsequently, disinhibits the release of dopamine. Moreover, it is argued that non-challenged high responders have a relatively low (alpha/beta) noradrenergic tonus that changes into a relatively high (alpha/beta) noradrenergic tonus during challenge, and that non-challenged low responders have a relatively high (alpha) adrenergic tonus that changes into a relatively low (alpha) noradrenergic tonus during challenge. In general, the present data clearly reveal that both alpha- and beta-adrenoceptors differentially regulate dopamine release in the nucleus accumbens. This regulation is individual-specific and depends on the test-condition (challenged versus non-challenged).
本研究的主要目标是提供体内神经化学证据，证明中脑边缘的α和β肾上腺素能受体指导中脑边缘多巴胺的释放。对新奇刺激反应高的大鼠和对新奇刺激反应低的大鼠均被用于研究在两种条件下，即静息状态（无刺激）和暴露于“新笼子”（刺激）时，向伏隔核内注射肾上腺素能药物对伏隔核中多巴胺释放的影响。在无刺激条件下：去氧肾上腺素（α肾上腺素能激动剂）引起多巴胺释放呈剂量依赖性增加，且在反应高的大鼠中增加幅度显著更大；酚妥拉明（α肾上腺素能受体拮抗剂）也引起多巴胺呈剂量依赖性增加，且在反应低的大鼠中增加幅度显著更大；异丙肾上腺素（β肾上腺素能激动剂）引起多巴胺呈剂量依赖性增加，两种类型的大鼠之间无差异；普萘洛尔（β肾上腺素能受体拮抗剂）未改变多巴胺释放。在刺激条件下：去氧肾上腺素和酚妥拉明均增加多巴胺释放，无类型特异性差异；只有在反应低的大鼠中，异丙肾上腺素增加了新奇刺激诱导的多巴胺释放；只有在反应高的大鼠中，普萘洛尔降低了新奇刺激诱导的多巴胺释放。结合早期报道的体外研究和药理行为学研究结果，对体内神经化学数据进行了讨论。总体而言，数据表明中脑边缘去甲肾上腺素在伏隔核中具有双重作用。有人认为，位于多巴胺神经末梢突触后的α肾上腺素能受体和β肾上腺素能受体的刺激分别抑制和促进多巴胺释放，而突触前α肾上腺素能受体的刺激抑制去甲肾上腺素释放，随后解除对多巴胺释放的抑制。此外，有人认为，无刺激时反应高的大鼠具有相对较低的（α/β）去甲肾上腺素能紧张性，在刺激过程中转变为相对较高的（α/β）去甲肾上腺素能紧张性，而无刺激时反应低的大鼠具有相对较高的（α）肾上腺素能紧张性，在刺激过程中转变为相对较低的（α）去甲肾上腺素能紧张性。一般来说，目前的数据清楚地表明，α和β肾上腺素能受体对伏隔核中多巴胺释放的调节存在差异。这种调节具有个体特异性，且取决于测试条件（刺激与无刺激）。
