Panlilio Leigh V, Hogarth Lee, Shoaib Mohammed
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, 21224, USA,
Psychopharmacology (Berl). 2015 Apr;232(8):1451-60. doi: 10.1007/s00213-014-3787-8. Epub 2014 Nov 1.
Animal models that allow concurrent access to drug and nondrug reinforcers provide unique insight into the etiology, maintenance, and treatment of drug use.
We sought to develop and utilize a concurrent access procedure with nicotine and sucrose in rats.
Pressing one lever delivered intravenous nicotine, and pressing another lever delivered sucrose pellets, with both reinforcers freely available throughout daily sessions.
Rats that had been pretrained with nicotine on some days and sucrose on other days responded on both levers when subsequently given concurrent access, but almost all responded at substantially higher rates on the sucrose lever. In contrast, rats pretrained exclusively with nicotine before being given concurrent access showed individual differences, with about half responding more on the nicotine lever. Treatment with the nicotinic receptor partial agonist varenicline selectively decreased nicotine self-administration. Food restriction and removal of the sucrose lever both increased nicotine self-administration.
The finding that rats continue to take nicotine when sucrose is concurrently available-and in many cases take it more frequently than sucrose-demonstrates that nicotine self-administration does not only occur in the absence of alternative reinforcement options. As a model of human nicotine use, concurrent access is more naturalistic and has higher face validity than procedures in which only one reinforcer is available or choosing one reinforcer precludes access to other reinforcers. As such, this procedure could be useful for evaluating therapeutic agents and improving our understanding of environmental conditions that promote or discourage nicotine use.
允许同时获取药物和非药物强化物的动物模型为药物使用的病因、维持和治疗提供了独特的见解。
我们试图开发并利用一种大鼠同时获取尼古丁和蔗糖的程序。
按压一个杠杆可静脉注射尼古丁,按压另一个杠杆可获得蔗糖颗粒,在每天的实验过程中两种强化物均可自由获取。
在某些日子用尼古丁预训练、其他日子用蔗糖预训练的大鼠,在随后同时获取两种强化物时会对两个杠杆都做出反应,但几乎所有大鼠对蔗糖杠杆的反应频率都显著更高。相比之下,在同时获取强化物之前仅用尼古丁预训练的大鼠表现出个体差异,约一半的大鼠对尼古丁杠杆的反应更多。用烟碱受体部分激动剂伐尼克兰治疗可选择性降低尼古丁自我给药。食物限制和移除蔗糖杠杆均增加了尼古丁自我给药。
当同时有蔗糖时大鼠仍会摄取尼古丁,并且在许多情况下摄取频率高于蔗糖,这一发现表明尼古丁自我给药并非仅在没有替代强化选择时才会发生。作为人类尼古丁使用的模型,同时获取强化物比仅有一种强化物可用或选择一种强化物就无法获取其他强化物的程序更符合实际情况且具有更高的表面效度。因此,该程序可能有助于评估治疗药物,并增进我们对促进或抑制尼古丁使用的环境条件的理解。