期刊
PSYCHOPHARMACOLOGY
卷 220, 期 1, 页码 43-54出版社
SPRINGER
DOI: 10.1007/s00213-011-2452-8
关键词
Acetylcholine; Dopamine; Intra-cranial self-administration; Nicotine; Pedunculopontine; Reinforcement; Reward; Ventral tegmental area
资金
- Wellcome Trust [066281]
- office of Deputy Principal Professor Keith Brown FRSE
Rationale 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. Objectives This study aimed to confirm previous data relating to intra-VTA self-administration of nicotine and carbachol and then test two hypotheses: (a) that presensitisation 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. Methods 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. Results 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. Conclusions 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.
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