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The Journal of Neuroscience, November 15, 2002, 22(22):9895-9904

Rewarding Effects of the Cholinergic Agents Carbachol and Neostigmine in the Posterior Ventral Tegmental Area

Satoshi Ikemoto and Roy A. Wise

Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224

Rats learned to lever-press for microinjections of the cholinergic agonist carbachol (30-500 pmol per infusion) or the acetylcholinesterase inhibitor neostigmine (7.5-75 pmol per infusion) into the posterior ventral tegmental area (VTA) of the brain. Intracranial carbachol self-administration was site-specific. Carbachol was not reliably self-administered into a site just dorsal to the VTA or into the adjacent substantia nigra and was self-administered only weakly into the adjacent anterior VTA or interpeduncular nucleus. Carbachol produced conditioned place preferences when injected into the posterior but not into the anterior VTA or sites dorsal to the posterior VTA. Rats self-administered carbachol less when it was co-infused with the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist dihydro--erythroidine, and also when the rats were pretreated with the D₁ dopamine antagonist SCH 23390. These findings implicate both nicotinic and muscarinic cholinergic neurotransmission in ventral tegmental reward function and suggest special involvement of the posterior portion of the VTA in cholinergic reward function.

Key words: reinforcement; self-administration; acetylcholine; nicotinic; muscarinic receptors; D₁ receptors; mesocorticolimbic dopamine neurons

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22229895-10$05.00/0

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