Cholinergic modulation of dopaminergic reward areas: upstream and downstream targets of nicotine addiction

H.D. Mansvelder, M. de Rover, D.S. McGehee, A.B. Brussaard

Research output: Contribution to JournalArticleAcademicpeer-review


Nicotine reinforces smoking behaviour by activating nicotinic acetylcholine receptors in the midbrain dopaminergic reward centres. Upstream of the dopaminergic neurons nicotine induces long-term potentiation of the excitatory input to dopamine cells in the ventral tegmental area, and depresses inhibitory inputs. Both effects of nicotine were shown to last much longer than the nicotine exposure and together will activate the dopaminergic ventral tegmental area projection toward the nucleus accumbens. However, downstream of dopamine, effects of nicotine are also likely to occur. Cholinergic interneurons within the nucleus accumbens are important in the tonic control of the γ-amino buteric acid (GABA) nucleus accumbens output neurons, which project back to the ventral tegmental area. The nicotinic acetylcholine receptors that mediate this control are likely to desensitise upon preexposure to the nicotine concentrations found in the blood of smokers. Thus, synaptic mechanisms both upstream and downstream of dopamine release are potentially important factors contributing to the etiology of nicotine addiction. © 2003 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)117-123
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - 2003


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