Morilak David A, Cecchi Marco, Khoshbouei Habibeh
Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, MC 7764, 7703 Floyd Curl Drive, 78229-3900, USA.
Life Sci. 2003 Jun 27;73(6):715-26. doi: 10.1016/s0024-3205(03)00392-8.
Many aspects of drug abuse and addiction share neurobiological substrates with the modulatory processes underlying the response and adaptation to acute stress. In particular, the ascending noradrenergic system has been implicated in facilitating the response to stress, and in stress-induced reinstatement of drug seeking behavior. Thus, to better understand the link between stress and addictive behaviors, it would be informative to understand better the modulatory function of the ascending noradrenergic system, and its interaction with other neurotransmitters with which it is closely associated or co-localized, such as the neuropeptide galanin. In this paper, we review a series of studies investigating the functional interactions of norepinephrine and galanin in modulating the behavioral response to acute stress in two components of the extended amygdala, the central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis. We showed that norepinephrine facilitates behavioral reactivity to stress on the elevated plus-maze and social interaction tests. However, when stress-induced activation of the noradrenergic system was enhanced by blocking inhibitory adrenergic autoreceptors, galanin release was recruited in the central amygdala, acting to attenuate the behavioral response to stress. By contrast, stress-induced galanin release in the lateral bed nucleus appeared to be independent of enhanced noradrenergic activation, and unlike the central amygdala, both galanin and norepinephrine facilitated behavioral stress reactivity in the bed nucleus. The different modes of interaction and differential region- and response-specificity of galanin and norepinephrine suggest that a complex neural circuit interconnecting these two regions is involved in the modulatory effects of norepinephrine and galanin on the behavioral response to stress. Such complexity may allow for flexibility and plasticity in stress adaptation, and may also contribute to behavioral changes induced by chronic drug administration. Thus, the interaction of galanin and norepinephrine may be a viable target for the future development of novel therapeutic strategies for treating behavioral disorders related to stress or drug abuse.
药物滥用和成瘾的许多方面与应对和适应急性应激的调节过程共享神经生物学底物。特别是，上行去甲肾上腺素能系统与促进对压力的反应以及压力诱导的觅药行为恢复有关。因此，为了更好地理解压力与成瘾行为之间的联系，更深入地了解上行去甲肾上腺素能系统的调节功能及其与其他紧密相关或共定位的神经递质（如神经肽甘丙肽）的相互作用将是很有意义的。在本文中，我们回顾了一系列研究，这些研究调查了去甲肾上腺素和甘丙肽在调节杏仁核扩展区的两个组成部分（杏仁核中央核和终纹床核外侧核）对急性应激的行为反应中的功能相互作用。我们发现，去甲肾上腺素在高架十字迷宫和社交互动测试中促进对压力的行为反应性。然而，当通过阻断抑制性肾上腺素能自身受体增强压力诱导的去甲肾上腺素能系统激活时，甘丙肽在杏仁核中央核释放，起到减弱对压力的行为反应的作用。相比之下，压力诱导的甘丙肽在终纹床核外侧核的释放似乎与增强的去甲肾上腺素能激活无关，并且与杏仁核中央核不同，甘丙肽和去甲肾上腺素都促进了终纹床核对行为应激的反应性。甘丙肽和去甲肾上腺素不同的相互作用模式以及区域和反应特异性表明，连接这两个区域的复杂神经回路参与了去甲肾上腺素和甘丙肽对压力行为反应的调节作用。这种复杂性可能允许在压力适应中具有灵活性和可塑性，也可能导致慢性药物给药引起的行为变化。因此，甘丙肽和去甲肾上腺素的相互作用可能是未来开发治疗与压力或药物滥用相关行为障碍的新治疗策略的可行靶点。
