Suárez M M, Rivarola M A, Molina S M, Levin G M, Enders J, Paglini P
Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
Stress. 2004 Sep;7(3):195-203. doi: 10.1080/10253890400010705.
Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or chronic stress also induced a long term anxiolytic effect, which was also not affected by ADTN lesion.
母婴分离会干扰大脑的生长和发育，是导致成人精神病理学的一个重要风险因素。在啮齿动物中，与母亲长期分离会影响动物一生对压力的行为和内分泌反应。诸如丘脑前背核（ADTN）等边缘结构在控制神经内分泌和交感 - 肾上腺功能方面发挥着重要作用。鉴于这些发现，我们推测在母婴剥夺动物模型中ADTN的功能可能会受到影响。为了验证这一假设，在出生后的前三周，每天将雌性大鼠隔离4.5小时，成年后进行测试。我们评估了ADTN损伤大鼠在母婴剥夺和可变慢性应激（VCS）后的血浆肾上腺素（E）和去甲肾上腺素（NE）、心脏肾上腺素能受体及焦虑反应。ADTN损伤30天后，在未经历母婴剥夺的大鼠中，基础血浆NE浓度更高，而心脏β - 肾上腺素能受体密度低于假损伤组。母婴剥夺导致基础血浆NE浓度显著升高，在损伤大鼠中更高，并且损伤大鼠的心脏β - 肾上腺素能受体密度降低。在VCS后，未经历母婴剥夺的大鼠血浆儿茶酚胺浓度比经历母婴剥夺的大鼠高得多；VCS使经历母婴剥夺和未经历母婴剥夺的大鼠的心脏β - 肾上腺素能受体密度均降低，但在未经历母婴剥夺的大鼠中降低得更多，并且ADTN损伤使其进一步降低。在高架十字迷宫试验中，经历母婴剥夺和应激的大鼠进入开放臂的次数更多。因此，VCS在未经历母婴剥夺的大鼠中产生的交感 - 肾上腺髓质激活作用更强，并且与心肌β - 肾上腺素能受体的下调有关。ADTN对母婴剥夺大鼠对应激时儿茶酚胺反应降低并不起作用。母婴剥夺或慢性应激还会诱导长期的抗焦虑作用，这也不受ADTN损伤的影响。
