Berridge C W, Mitton E, Clark W, Roth R H
Psychology Department, University of Wisconsin, Madison 53706-1611, USA.
Synapse. 1999 Jun 1;32(3):187-97. doi: 10.1002/(SICI)1098-2396(19990601)32:3<187::AID-SYN5>3.0.CO;2-9.
Although the preferential activation of the prefrontal cortical (PFC) dopaminergic system is generally observed in stress, limited exceptions to this have been observed. Certain non-escape behaviors have been demonstrated to attenuate physiological indices of stress (e.g., coping or displacement responses). One well-characterized non-escape behavior observed in stress is chewing, or gnawing, of inedible objects. Engagement in this behavior attenuates stress-related activation of the hypothalamopituitary-adrenal axis, in a variety of species. We examined the degree to which engagement in this non-escape behavior modulates stressor-induced activation of the PFC dopamine (DA) system. Rats and mice were exposed to a brightly lit novel environment (novelty stress) in the presence or absence of inedible objects. Following novelty exposure, various dopaminergic terminal fields were collected and dopamine and its major catabolite, DOPAC, were measured using HPLC with electrochemical detection. DOPAC/DA ratios were calculated as an index of DA utilization. In some cases serotonin (5-HT) and its major catabolite, 5-HIAA, were also measured. In animals that did not chew, novelty exposure elicited significant increases in DOPAC/DA levels within PFC, nucleus accumbens (shell and core subdivisions), and striatum (relative to quiet-controls). DOPAC/DA responses were greater in the right PFC than in the left PFC. Animals that chewed displayed significantly lower DOPAC/DA responses in PFC, but not other dopaminergic terminal fields. This effect of chewing was always observed in the right PFC and less consistently in the left PFC. Chewing did not alter novelty-induced increases in PFC 5-HIAA/5-HT responses. Thus, engagement in this non-escape behavior elicits a neuroanatomically and neurochemically specific attenuation of the PFC DA response in stress. Given the pivotal role of the PFC in certain cognitive and affective processes, behavioral regulation of PFC DA utilization may modulate cognitive and/or affective function in stress.
尽管在应激状态下通常会观察到前额叶皮质（PFC）多巴胺能系统的优先激活，但也有一些有限的例外情况。某些非逃避行为已被证明可减轻应激的生理指标（例如应对或替代反应）。在应激状态下观察到的一种特征明确的非逃避行为是咀嚼或啃咬不可食用的物体。在多种物种中，参与这种行为会减弱下丘脑-垂体-肾上腺轴的应激相关激活。我们研究了参与这种非逃避行为对应激源诱导的PFC多巴胺（DA）系统激活的调节程度。将大鼠和小鼠置于有或没有不可食用物体的明亮新奇环境中（新奇应激）。新奇暴露后，收集各种多巴胺能终末场，并使用高效液相色谱电化学检测法测量多巴胺及其主要代谢产物3,4-二羟基苯乙酸（DOPAC）。计算DOPAC/DA比率作为DA利用的指标。在某些情况下，还测量了5-羟色胺（5-HT）及其主要代谢产物5-羟吲哚乙酸（5-HIAA）。在不咀嚼的动物中，新奇暴露会导致PFC、伏隔核（壳和核心亚区）和纹状体中DOPAC/DA水平显著升高（相对于安静对照组）。右侧PFC中的DOPAC/DA反应比左侧PFC中的更大。咀嚼的动物在PFC中显示出显著更低的DOPAC/DA反应，但在其他多巴胺能终末场中则没有。这种咀嚼效应总是在右侧PFC中观察到，而在左侧PFC中则不太一致。咀嚼并未改变新奇诱导的PFC中5-HIAA/5-HT反应的增加。因此，参与这种非逃避行为会在应激状态下引发PFC DA反应在神经解剖学和神经化学上的特异性减弱。鉴于PFC在某些认知和情感过程中的关键作用，PFC DA利用的行为调节可能会调节应激状态下的认知和/或情感功能。
