Pituitary Adenylate Cyclase-Activating Polypeptide Disrupts Motivation, Social Interaction, and Attention in Male Sprague Dawley Rats
Pituitary Adenylate Cyclase-Activating Polypeptide Disrupts Motivation, Social Interaction, and Attention in Male Sprague Dawley Rats
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DOI：
10.1016/j.biopsych.2015.06.013
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发表时间：
2016-12-15
影响因子：
10.6
通讯作者：
Carlezon, William A., Jr.
中科院分区：
文献类型：
--
作者：
Donahue, Rachel J.;Venkataraman, Archana;Carlezon, William A., Jr.
背景：严重或长期的压力可以引发精神疾病，包括情绪和焦虑症。近年来的研究表明，垂体腺苷酸环化酶激活多肽（PACAP）在应激反应中起重要的调节作用。在啮齿类动物中，外源性PACAP给药可导致声惊吓反应持续升高，这可能反映了焦虑样体征，包括过度警觉。我们调查是否PACAP引起急性或持续性的行为改变，反映其他核心特征的情绪和焦虑症（动机，社会交往，和attention）。方法：使用雄性Sprague道利大鼠，我们研究了如果PACAP（0.25 -1.0 μ g，脑室内灌注）影响动机在颅内自我刺激测试。我们还研究了PACAP是否会改变与同种在社会互动测试的相互作用。最后，我们研究了PACAP是否会影响5-选择系列反应时间任务的性能，该任务量化了注意力和错误processing.RESULTS：剂量依赖性中断的动机，社会交往和注意力产生的PACAP，反映在奖励阈值的增加，减少社会行为，并减少正确的反应和改变postterror准确性。在颅内自我刺激和5选择系列反应时间任务测试中，行为迅速正常化，但在社交互动测试中仍然失调。促肾上腺皮质激素释放因子受体-1拮抗剂antalarmin减弱了对注意力的影响，但没有。阿片受体拮抗剂JDTic。结论：我们的研究结果表明，PACAP影响许多领域往往失调的情绪和焦虑症，但个别迹象取决于大脑基板，至少部分独立。这项工作可能有助于设计减轻这些疾病的特定症状的治疗方法。
BACKGROUND: Severe or prolonged stress can trigger psychiatric illnesses including mood and anxiety disorders. Recent work indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in regulating stress effects. In rodents, exogenous PACAP administration can produce persistent elevations in the acoustic startle response, which may reflect anxiety-like signs including hypervigilance. We investigated whether PACAP causes acute or persistent alterations in behaviors that reflect other core features of mood and anxiety disorders (motivation, social interaction, and attention).METHODS: Using male Sprague Dawley rats, we examined if PACAP (.25-1.0 mu g, intracerebroventricular infusion) affects motivation as measured in the intracranial self-stimulation test. We also examined if PACAP alters interactions with a conspecific in the social interaction test. Finally, we examined if PACAP affects performance in the 5-choice serial reaction time task, which quantifies attention and error processing.RESULTS: Dose-dependent disruptions in motivation, social interaction, and attention were produced by PACAP, as reflected by increases in reward thresholds, decreases in social behaviors, and decreases in correct responses and alterations in posterror accuracy. Behavior normalized quickly in the intracranial self-stimulation and 5-choice serial reaction time task tests but remained dysregulated in the social interaction test. Effects on attention were attenuated by the corticotropin-releasing factor receptor-1 antagonist antalarmin but not the. opioid receptor antagonist JDTic.CONCLUSIONS: Our findings suggest that PACAP affects numerous domains often dysregulated in mood and anxiety disorders, but that individual signs depend on brain substrates that are at least partially independent. This work may help to devise therapeutics that mitigate specific signs of these disorders.