Nicotine self-administered directly into the VTA by rats is weakly reinforcing but has strong reinforcement enhancing properties
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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.
KeywordsAcetylcholine Dopamine Intra-cranial self-administration Nicotine Pedunculopontine Reinforcement Reward Ventral tegmental area
These experiments were conducted in the School of Psychology, University of St Andrews. Initial work was supported by Wellcome Trust project grant 066281 to PW. We acknowledge the support to MJF in St Andrews given through the office of Deputy Principal Professor Keith Brown FRSE and the helpful advice of Duncan MacLaren and Dr Alan Sved. We also gratefully acknowledge the invaluable assistance of Dr Satoshi Ikemoto and Med Associates Inc. in establishing ICSA in our lab.
Disclosure/conflicts of interest
The authors have no disclosures.
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