Barr Christina S, Newman Timothy K, Shannon Courtney, Parker Clarissa, Dvoskin Rachel L, Becker Michelle L, Schwandt Melanie, Champoux Maribeth, Lesch Klaus Peter, Goldman David, Suomi Stephen J, Higley J Dee
Laboratory of Clinical Studies, National Institute of Alcoholism and Alcohol Abuse, National Institutes of Health, Poolesville, Maryland 20837, USA.
Biol Psychiatry. 2004 Apr 1;55(7):733-8. doi: 10.1016/j.biopsych.2003.12.008.
In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety. Serotonin transporter gene disruption in rodents produces anxious animals with exaggerated limbic-hypothalamic-pituitary-adrenal (LHPA) responses to stress. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence endocrine responses to stress in infant rhesus macaques.
Animals were reared with their mothers (MR, n = 141) or in peer-only groups (PR, n = 67). At 6 months of age, adrenocorticotropic hormone (ACTH) and cortisol levels were determined at baseline and during separation stress. Serotonin transporter genotype (l/l and l/s) was determined with polymerase chain reaction followed by gel electrophoresis.
Cortisol levels increased during separation, and there was a main effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with l/s rh5-HTTLPR genotypes had higher ACTH levels than did l/l animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation x rearing x rh5-HTTLPR interaction, such that PR-l/s animals had higher ACTH levels during separation than did other animals studied.
These data demonstrate that serotonin transporter gene variation affects LHPA axis activity and that the influence of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.
在人类和猕猴中，一种降低血清素转运体基因转录的启动子多态性与焦虑有关。啮齿动物中血清素转运体基因的破坏会产生对应激有过度边缘 - 下丘脑 - 垂体 - 肾上腺（LHPA）反应的焦虑动物。我们想确定血清素转运体基因启动子变异（rh - 5HTTLPR）和饲养条件是否会相互作用，影响幼年恒河猴对应激的内分泌反应。
动物与母亲一起饲养（MR，n = 141）或仅与同伴在群体中饲养（PR，n = 67）。在6个月大时，在基线和分离应激期间测定促肾上腺皮质激素（ACTH）和皮质醇水平。通过聚合酶链反应随后进行凝胶电泳确定血清素转运体基因型（l/l和l/s）。
分离期间皮质醇水平升高，饲养条件有主要影响，PR猕猴的皮质醇水平降低。具有l/s rh5 - HTTLPR基因型的动物比l/l动物的ACTH水平更高。分离期间促肾上腺皮质激素水平升高，并且存在分离×饲养×rh5 - HTTLPR相互作用，使得PR - l/s动物在分离期间的ACTH水平高于其他研究的动物。
这些数据表明血清素转运体基因变异会影响LHPA轴活性，并且rh5 - HTTLPR对应激期间激素反应的影响受早期经历调节。
