Kawakami Suzi Emiko, Quadros Isabel Marian Hartmann, Takahashi Shirley, Suchecki Deborah
Department of Psychobiology, Universidade Federal de São Paulo, Brazil.
Behav Brain Res. 2007 Dec 3;184(2):109-16. doi: 10.1016/j.bbr.2007.06.023. Epub 2007 Jul 1.
Early life stress is associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and with aspects involved in drug abuse. In this study, we investigated the effects of brief (BMS) and long maternal separation (LMS) on the HPA axis response and behavioural sensitization to ethanol (EtOH) in male and female mice. From PND 2 to 14, pups were subjected to daily maternal separation for 15 min (BMS) or 180 min (LMS) or no separated, only handled during cage cleaning (animal facility rearing-AFR). As adults, animals were treated every other day with saline (SAL) or EtOH (2.2g/kg), i.p., for 10 days, and immediately after each administration, their locomotor response was evaluated for 15 min. Forty-eight hours after the 5th administration, all animals were challenged with saline, followed 48 h later, by an EtOH challenge. Corticosterone (CORT) plasma levels were determined 3 times: basal, after the 1st administration and after the EtOH challenge. LMS females showed higher CORT levels than BMS females at basal, but not in response to acute or chronic EtOH administration. The CORT response to EtOH was more robust in LMS and BMS male than AFR male mice. Repeated EtOH treatment induced behavioural sensitization in all groups of male mice. In females, LMS induced a faster sensitization, although BMS females also exhibited behavioural sensitization (4th day and 5th day of treatment, respectively). In conclusion, LMS and BMS produced gender-dependent effects. In females, LMS and BMS facilitated the development of behavioural sensitization, but in the LMS group this effect occurred faster, which may represent increased vulnerability to drug abuse. Moreover, LMS females showed higher basal CORT levels compared to BMS. In males, LMS and BMS increased the CORT response to EtOH but did not modify behavioural sensitization. Therefore, we postulate that LMS female mice exhibited a faster development of behavioural sensitization, but CORT levels were not involved with this effect.
早年生活应激与下丘脑-垂体-肾上腺（HPA）轴功能障碍以及药物滥用所涉及的方面有关。在本研究中，我们调查了短期（BMS）和长期母婴分离（LMS）对雄性和雌性小鼠HPA轴反应以及对乙醇（EtOH）行为敏化的影响。从出生后第2天到第14天，幼崽每天接受15分钟（BMS）或180分钟（LMS）的母婴分离，或不分离，仅在笼舍清洁时处理（动物设施饲养-AFR）。成年后，动物每隔一天腹腔注射生理盐水（SAL）或EtOH（2.2g/kg），持续10天，每次给药后立即评估其运动反应15分钟。第5次给药后48小时，所有动物用生理盐水进行激发，48小时后再用EtOH进行激发。测定血浆皮质酮（CORT）水平3次：基础水平、第1次给药后以及EtOH激发后。基础水平时，LMS雌性小鼠的CORT水平高于BMS雌性小鼠，但对急性或慢性EtOH给药无反应。LMS和BMS雄性小鼠对EtOH的CORT反应比AFR雄性小鼠更强烈。重复EtOH处理在所有雄性小鼠组中均诱导了行为敏化。在雌性小鼠中，LMS诱导的敏化更快，尽管BMS雌性小鼠也表现出行为敏化（分别在治疗的第4天和第5天）。总之，LMS和BMS产生了性别依赖性效应。在雌性小鼠中，LMS和BMS促进了行为敏化的发展，但在LMS组中这种效应出现得更快，这可能代表对药物滥用的易感性增加。此外，与BMS相比，LMS雌性小鼠的基础CORT水平更高。在雄性小鼠中，LMS和BMS增加了对EtOH的CORT反应，但未改变行为敏化。因此，我们推测LMS雌性小鼠行为敏化的发展更快，但CORT水平与这种效应无关。
