Strathclyde Institute of Pharmacy & Biomedical Science, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
Psychopharmacology (Berl). 2012 Mar;220(1):43-54. doi: 10.1007/s00213-011-2452-8. Epub 2011 Sep 6.
Rats will lever press to deliver nanolitre quantities of nicotine or the muscarinic agonist carbachol directly into the ventral tegmental area (VTA). The purpose of these experiments was to investigate further the characteristics of nicotine self-administration directly into the VTA.
This study aimed to confirm previous data relating to intra-VTA self-administration of nicotine and carbachol and then test two hypotheses: (a) that pre-sensitisation of nicotinic receptors is needed for robust intra-VTA self administration and (b) that rats will lever press for intra-VTA nicotine if pre-trained to associate lever pressing with a rewarding outcome.
Rats were equipped with cannulae aimed at posterior VTA and allowed five sessions to self-administer nicotine or carbachol. In different experiments, rats were either pre-sensitised to nicotine by subcutaneous (s.c.) injections or pre-trained to lever press for food and a simultaneous conditioned stimulus light.
We confirmed that carbachol had strong activating effects when self-administered into the VTA; selective responding for nicotine developed over five sessions by reduction in the amount of pressing on an inactive lever. Prior sensitisation did not improve responding for intra-VTA nicotine but training rats to lever press before putting them on the drug regime did potentiate pressing.
The action of nicotine in the VTA might be better considered as reinforcement enhancing and that its intrinsic rewarding property here is at best weak. Identification of the VTA as a target for the reinforcement enhancing effects of nicotine is compatible with the reinforcement-related functions of VTA dopamine neurons and their cholinergic inputs.
老鼠会按压杠杆,将纳升级数量的尼古丁或毒蕈碱激动剂 carbachol 直接输送到腹侧被盖区 (VTA)。这些实验的目的是进一步研究直接在 VTA 中给予尼古丁自我给药的特征。
本研究旨在证实先前与 VTA 内尼古丁和 carbachol 自我给药有关的数据,然后检验两个假设:(a) 尼古丁受体的预敏化对于强大的 VTA 内自我给药是必要的;(b) 如果预先训练大鼠将按压杠杆与奖励性结果联系起来,那么它们将按压杠杆来获取 VTA 内的尼古丁。
给大鼠配备了针对 VTA 后区的导管,并允许它们进行五次自行注射尼古丁或 carbachol 的实验。在不同的实验中,大鼠要么通过皮下 (s.c.) 注射预先敏化尼古丁,要么预先训练按压杠杆以获得食物和同时的条件性刺激光。
我们证实了 carbachol 在 VTA 内自我给药时具有强烈的激活作用;通过减少对非活动杠杆的按压量,选择性地对尼古丁产生反应。预先敏化并没有改善对 VTA 内尼古丁的反应,但在给大鼠进行药物治疗之前对其进行按压杠杆训练会增强按压反应。
VTA 中尼古丁的作用可能更好地被认为是增强强化作用,而其内在的奖励性质充其量是微弱的。将 VTA 确定为尼古丁增强强化作用的靶点与 VTA 多巴胺神经元及其胆碱能输入的强化相关功能是一致的。