STRESS-INDUCED SICKNESS BEHAVIOR DURING SEPARATION

描述(申请人提供)：在某些种类的灵长类动物和豚鼠中，婴儿在母体分离期间表现出两个阶段的主动/被动反应。这种从母性依恋中分离出来的第二阶段(在灵长类动物中称为绝望)为抑郁症的研究提供了一个长期存在的动物模型。拟议的实验将在豚鼠幼鼠身上检验以下假设：(1)在长时间隔离期间观察到的被动行为(蹲立、闭眼、广泛竖立，以及低水平的发声和运动活动)代表已被称为“应激诱导的疾病行为”(即，可由应激源和免疫刺激引发的炎症反应的组成部分)；以及(2)应激反应肽CRF可以刺激炎症反应，从而产生被动行为反应。具体目标1将评估第一个假设，试图通过以下方法逆转在隔离的豚鼠幼鼠中观察到的被动行为反应和核心温度升高：(1)向大脑通气孔注入抗炎肽α-MSH；(2)全身应用前列腺素合成抑制剂吲哚美辛。《特定目标2》将通过使用相同的两种技术来评估第二种假设，试图逆转注射CRF所产生的被动行为反应。拟议研究中的积极结果将提供另一种视角来看待经典的母体分离反应的要素，并将支持最近将抑郁症状的各个方面概念化为炎症反应的行为成分。

DESCRIPTION (provided by applicant): In some species of primates as well as guinea pigs, infants exhibit a 2-stage, active/passive, response during maternal separation. This second stage (termed despair in primates) of separation from the maternal attachment figure has provided a long-standing animal model for the study of depressive illness. The proposed experiments will test in guinea pig pups the hypotheses that: (1) passive behaviors (crouched stance, eye-closing, and extensive piloerection together with low levels of vocalizing and locomotor activity) observed during prolonged isolation represent what have come to be known as "stress-induced sickness behaviors" (i.e., components of the inflammatory response that can be elicited by stressors as well as immunologic stimuli); and, (2) that the stress-responsive peptide CRF can stimulate inflammatory reactions to produce the passive behavioral responses. Specific Aim 1 will evaluate the first hypothesis by attempting to reverse the passive behavioral responses and increased core temperature observed in isolated guinea pig pups with: (1) infusion into the cerebral venticles of alpha-MSH, an anti-inflammatory peptide; and, (2) systemic administration of indomethacin, an inhibitor of prostaglandin synthesis. Specific Aim 2 will evaluate the second hypothesis by using the same two techniques to attempt to reverse passive behavioral responses produced by injection of CRF. Positive results in the proposed studies would provide an alternative perspective from which to view elements of the classic maternal separation response and would support recent conceptualizations of aspects of depressive symptomatology as behavioral components of the inflammatory response.