Echevarria David J, Hernandez Angelica, Diogenes Anibal, Morilak David A
Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, United States.
Neuropeptides. 2005 Oct;39(5):445-51. doi: 10.1016/j.npep.2005.06.004. Epub 2005 Aug 9.
Galanin (GAL) has been implicated in modulating anxiety, although a precise role remains unclear. Previous studies revealed anxiolytic effects, anxiogenic effects, or no effect, depending on the test, brain region, route of drug administration and context. We have shown previously that microinjection of the GAL antagonist M40 into central amygdala blocked an anxiolytic response to acute stress on the elevated plus maze when rats were pretreated with yohimbine, suggesting an anxiolytic effect of GAL. By contrast, we also showed that microinjection of M40 into the lateral bed nucleus of the stria terminalis attenuated anxiety-like behavioral responses to stress on the plus maze and social interaction tests, implying an anxiogenic effect for GAL. The behavioral response to stress on both these tests is a reduction of an ongoing behavior (open-arm exploration or social interaction, respectively). To better understand the anxiety-modulating role of GAL, it is also important to ascertain its effect on a response that represents an activation rather than suppression of behavior. Thus, in this study, we investigated an active behavioral response to acute stress in rats, the shock-probe defensive burying response. Bilateral microinjections of M40 into lateral septum (LS), a region important to this response and innervated by GAL, dose-dependently decreased burying without affecting immobility. No change was seen in hindpaw withdrawal latency on a thermosensitivity assay, suggesting that the reduction in burying behavior was not attributable to changes in cutaneous pain sensitivity. These results indicate that in LS, GAL facilitates the active anxiety-like behavioral response on the defensive burying test, similar to its facilitatory effect on anxiety-like stress-induced suppression of behavior in the lateral bed nucleus. These results highlight the fact that, rather than a unified system-like role in modulating anxiety, the effects of GAL can be either facilitating or attenuating, and are region-specific, context-specific and response-specific.
甘丙肽（GAL）与焦虑调节有关，但其确切作用尚不清楚。先前的研究根据测试、脑区、给药途径和背景情况，揭示了其抗焦虑作用、致焦虑作用或无作用。我们之前已经表明，当大鼠用育亨宾预处理后，向中央杏仁核微量注射GAL拮抗剂M40可阻断高架十字迷宫中对急性应激的抗焦虑反应，提示GAL具有抗焦虑作用。相比之下，我们还表明，向终纹床核外侧微量注射M40可减弱在十字迷宫和社交互动测试中对应激的焦虑样行为反应，这意味着GAL有致焦虑作用。在这两种测试中对应激的行为反应都是正在进行的行为（分别为开放臂探索或社交互动）减少。为了更好地理解GAL在焦虑调节中的作用，确定其对代表行为激活而非抑制的反应的影响也很重要。因此，在本研究中，我们研究了大鼠对急性应激的主动行为反应，即电击探针防御性埋土反应。向外侧隔区（LS）双侧微量注射M40，该区域对这种反应很重要且受GAL支配，剂量依赖性地减少了埋土行为，而不影响不动时间。在热敏感性测定中后爪退缩潜伏期没有变化，这表明埋土行为的减少不是由于皮肤疼痛敏感性的变化。这些结果表明，在LS中，GAL促进了防御性埋土测试中的主动焦虑样行为反应，类似于其对终纹床核外侧焦虑样应激诱导的行为抑制的促进作用。这些结果突出了这样一个事实，即GAL的作用不是在调节焦虑方面具有统一的系统样作用，而是既可以促进也可以减弱，并且是区域特异性、背景特异性和反应特异性的。
