Morrison T R, Sikes R W, Melloni R H
Behavioral Neuroscience Program, Department of Psychology, Northeastern University, Boston, MA 02115, United States.
Department of Physical Therapy, Rehabilitation, and Movement Sciences, Northeastern University, Boston, MA 02115, United States.
Neuroscience. 2016 Feb 19;315:1-17. doi: 10.1016/j.neuroscience.2015.12.001. Epub 2015 Dec 10.
Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.
在多项研究中,青春期接触合成代谢/雄激素类固醇(AAS)的叙利亚仓鼠始终表现出攻击性行为增加。尽管AAS诱导的改变的行为和解剖学特征已得到充分描述,但缺乏描述伴随这些改变的生理变化的数据。例如,行为药理学和神经解剖学研究表明,AAS诱导的下丘脑前外侧(LAH)内血管加压素(AVP)神经系统的变化与血清素(5HT)和多巴胺(DA)系统相互作用以调节攻击性。为了表征AAS攻击回路的电生理特征,我们在体内记录了青春期雄性仓鼠的LAH神经元,并通过微离子电泳应用攻击性行为的激动剂和拮抗剂。来自接受AAS治疗动物的神经元的峰间间隔(ISI)与攻击性行为呈正相关,青春期接触AAS改变了正常放电神经元的活动参数,同时也改变了神经元类型的比例(即爆发性、正常、不规则)。接受AAS治疗的动物有更多对AVP应用有反应的兴奋性神经元,而对照动物的细胞则表现出相反的效果,主要被AVP抑制。DA D2拮抗剂和5HT都增加了来自AAS动物的AVP反应性细胞的放电频率,AVP和D2拮抗剂的联合应用使单独应用AVP或D2拮抗剂的兴奋作用加倍。这些数据表明,LAH中的多个DA回路调节AAS诱导的攻击反应。更广泛地说,这些数据表明,青春期接触AAS会改变神经生理水平上的多种神经化学相互作用。