Contreras Marco, Riveros María E, Quispe Maricel, Sánchez Cristián, Perdomo Guayec, Torrealba Fernando, Valdés José L
Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Centro de Fisiología Celular Integrativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo. Santiago, Chile.
PLoS One. 2016 Feb 4;11(2):e0148484. doi: 10.1371/journal.pone.0148484. eCollection 2016.
The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24 h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors.
组胺能系统是上行觉醒系统的一个组成部分,参与清醒、神经内分泌控制、认知、精神疾病和动机等过程。在动机行为的欲求阶段,觉醒状态会上升到最佳水平,从而使行为具有适当的强度。先前的研究表明,与其他上行觉醒系统核相比,组胺能神经元在进食的欲求阶段表现出更早的激活,同时觉醒状态也会大幅上升。与完整或假损伤的大鼠相比,限制大鼠组胺能神经元的损伤即使在禁食24小时后也会降低它们获取食物的动机。综上所述,这些发现表明组胺能系统对与进食相关的欲求行为很重要。然而,其在其他目标导向行为中的作用仍未得到探索。在本研究中,有获取水、性或安非他命动机的雄性大鼠在获取这些强化物的欲求行为中,组胺能神经元的Fos免疫反应性增加。然而,在获取性或安非他命条件化大鼠的药物的欲求测试中,Fos表达在大多数其他上行觉醒系统核中增加,包括下丘脑外侧的食欲素神经元、中缝背核、蓝斑和外侧背盖神经元,但腹侧被盖区没有增加,在这三种条件下均未显示Fos免疫反应性增加。重要的是,在组胺能细胞特异性损伤后,所有这些欲求行为都大幅减少,这表明组胺对几种欲求行为的强度成分有重要贡献。