Olsen Christopher M, Winder Danny G
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Neuropsychopharmacology. 2009 Jun;34(7):1685-94. doi: 10.1038/npp.2008.226. Epub 2009 Jan 14.
Novelty and sensation seeking have been associated with elevated drug intake in human and animal studies, suggesting overlap in the circuitry mediating these behaviors. In this study, we found that C57Bl/6J mice readily acquired operant responding for dynamic visual stimuli, a phenomenon we term operant sensation seeking (OSS). Like operant studies using other reinforcers, mice responded on fixed and progressive ratio schedules, were resistant to extinction, and had sustained responding with extended access. We also found that OSS, like psychostimulant self-administration, is sensitive to disruption of dopamine signaling. Low doses of the dopamine antagonist cis-flupenthixol increased active lever responding, an effect reported for psychostimulant self-administration. Additionally, D1-deficient mice failed to acquire OSS, although they readily acquired lever pressing for food. Finally, we found that one common measure of novelty seeking, locomotor activity in a novel open field, did not predict OSS performance. OSS may have predictive validity for screening compounds for use in the treatment of drug addiction. In addition, we also discuss the potential relevance of this animal model to the field of behavioral addictions.
在人类和动物研究中,新奇感和寻求刺激与药物摄入量增加有关,这表明介导这些行为的神经回路存在重叠。在本研究中,我们发现C57Bl/6J小鼠很容易为动态视觉刺激而习得操作性反应,我们将这一现象称为操作性寻求刺激(OSS)。与使用其他强化物的操作性研究一样,小鼠在固定比率和累进比率时间表上做出反应,对消退有抵抗力,并且在延长接触时间时持续做出反应。我们还发现,OSS与精神兴奋剂自我给药一样,对多巴胺信号的破坏敏感。低剂量的多巴胺拮抗剂顺式氟哌噻吨增加了主动杠杆反应,这一效应在精神兴奋剂自我给药中也有报道。此外,D1基因缺陷小鼠未能习得OSS,尽管它们很容易习得为获取食物而按压杠杆。最后,我们发现寻求新奇感的一个常见指标,即在新颖开阔场地中的运动活动,并不能预测OSS表现。OSS可能对筛选用于治疗药物成瘾的化合物具有预测效度。此外,我们还讨论了这种动物模型与行为成瘾领域的潜在相关性。