Kawakami Suzi E, Quadros Isabel M H, Suchecki Deborah
Department of Psychobiology, Escola Paulista de Medicina - Universidade Federal de São Paulo (UNIFESP) , Sao Paulo , Sao Paulo, Brazil.
Front Endocrinol (Lausanne). 2016 Oct 18;7:135. doi: 10.3389/fendo.2016.00135. eCollection 2016.
Maternal separation alters the activity of the opioid system, which modulates ethanol-induced stimulation and behavioral sensitization. This study examined the effects of an opioid antagonist, naltrexone (NTX), on the expression of behavioral sensitization to ethanol in adult male and female mice submitted to maternal separation from postnatal days (PNDs) 2 to 14. Whole litters of Swiss mice were either not separated [animal facility rearing (AFR)] or separated from their mothers for 3 h [long maternal separation (LMS)]. Starting on PND 90, male and female AFR and LMS mice received daily i.p. injections of saline (SAL) or ethanol (EtOH, 2.2 g/kg) for 21 days. Locomotor activity was assessed in cages containing photoelectric beams, once a week, to examine the development of behavioral sensitization. Five days after the end of the chronic treatment, animals were submitted to four locomotor activity tests spaced by 48 h, to assess the expression of behavioral sensitization. In all tests, animals received two i.p. injections with a 30-min interval and were then assessed for locomotor response to different treatment challenges, which were: SAL/SAL, SAL/EtOH (2.2 g/kg), NTX 2.0 mg/kg (NTX2)/EtOH, and NTX 4.0 mg/kg (NTX4)/EtOH. Regardless of maternal separation, EtOH-treated male and female mice displayed increased locomotor responses to EtOH during the 21-day treatment, indicating the development of behavioral sensitization. In the SAL/EtOH challenge, EtOH-treated LMS and AFR male and female mice exhibited higher locomotor activity than their SAL-treated counterparts, indicating the expression of sensitization. The coadministration of either dose of NTX blocked the expression of locomotor sensitization in both AFR and LMS male mice with a history of EtOH sensitization. In females, a significant attenuation of EtOH sensitization was promoted by both NTX doses, while still maintaining an augmented stimulant response to EtOH. Importantly, maternal separation did not interfere in this phenomenon. These results indicate that expression of behavioral sensitization was importantly modulated by opioidergic mechanisms both in male and female mice and that maternal separation did not play a major role in either development or expression of this EtOH sensitization.
母婴分离会改变阿片系统的活性，而该系统可调节乙醇诱导的刺激和行为敏化。本研究检测了阿片拮抗剂纳曲酮（NTX）对出生后第2天至第14天经历母婴分离的成年雄性和雌性小鼠乙醇行为敏化表达的影响。将瑞士小鼠的整窝幼崽分为不分离组[动物设施饲养（AFR）]或与母亲分离3小时组[长时间母婴分离（LMS）]。从出生后第90天开始，AFR和LMS组的雄性和雌性小鼠每天腹腔注射生理盐水（SAL）或乙醇（EtOH，2.2 g/kg），持续21天。每周一次在装有光电束的笼子里评估运动活性，以检测行为敏化的发展情况。慢性治疗结束后5天，对动物进行4次间隔48小时的运动活性测试，以评估行为敏化的表达。在所有测试中，动物腹腔注射两次，间隔30分钟，然后评估其对不同处理挑战的运动反应，这些挑战包括：SAL/SAL、SAL/EtOH（2.2 g/kg）、NTX 2.0 mg/kg（NTX2）/EtOH和NTX 4.0 mg/kg（NTX4）/EtOH。无论是否经历母婴分离，接受乙醇处理的雄性和雌性小鼠在21天的处理过程中对乙醇的运动反应均增加，表明行为敏化的发展。在SAL/EtOH挑战中，接受乙醇处理的LMS和AFR组雄性和雌性小鼠的运动活性高于接受生理盐水处理的对应组，表明敏化的表达。两种剂量NTX与乙醇共同给药均阻断了有乙醇敏化史的AFR和LMS组雄性小鼠的运动敏化表达。在雌性小鼠中，两种剂量的NTX均显著减弱了乙醇敏化，但对乙醇的刺激反应仍增强。重要的是，母婴分离并未干扰这一现象。这些结果表明，行为敏化的表达在雄性和雌性小鼠中均受到阿片能机制的重要调节，且母婴分离在这种乙醇敏化的发展或表达中均未起主要作用。
