Cholinergic functioning in stimulant addiction: Implications for medications development

Mehmet Sofuoglu, Marc E Mooney

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations


Acetylcholine, the first neurotransmitter discovered, participates in many CNS functions, including sensory and motor processing, sleep, nociception, mood, stress response, attention, arousal, memory, motivation and reward. These diverse cholinergic effects are mediated by nicotinic-and muscarinic-type cholinergic receptors (nAChR and mAChR, respectively). The goal of this review is to synthesize a growing literature that supports the potential role of acetylcholine as a treatment target for stimulant addiction. Acetylcholine interacts with the dopaminergic reward system in the ventral tegmental area, nucleus accumbens and prefrontal cortex. In the ventral tegmental area, both nAChR and mAChR stimulate the dopaminergic system. In the nucleus accumbens, cholinergic interneurons integrate cortical and subcortical information related to reward. In the prefrontal cortex, the cholinergic system contributes to the cognitive aspects of addiction. Preclinical studies support a facilitative role of nicotinic receptor agonists in the development of stimulant addiction. In contrast, nonselective muscarinic receptor agonists seem to have an inhibitory role. In human studies, acetylcholinesterase inhibitors, which increase synaptic acetylcholine levels, have shown promise for the treatment of stimulant addiction. Further studies testing the efficacy of cholinergic medications for stimulant addiction are warranted.

Original languageEnglish (US)
Pages (from-to)939-952
Number of pages14
JournalCNS Drugs
Issue number11
StatePublished - 2009

Bibliographical note

Funding Information:
The authors were supported by career development awards, K02-DA021304 (MS) and K01-DA019446 (MM), by RO1DA019885, RO1DA020752, RO1DA014537 and the Veterans Administration Mental Illness Research, Education and Clinical Center (MIRECC). The authors have no conflicts of interest that are directly relevant to the content of this review.


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