TY - JOUR
T1 - The role of acetylcholine in cocaine addiction
AU - Williams, Mark J.
AU - Adinoff, Bryon
N1 - Funding Information:
This work was funded, in part, by the National Institute on Drug Abuse Grant DA11434 and supported by the VA North Texas Health Care System. Disclosures (payment for professional services): Dr Adinoff has received compensation for consultation from GSK and Pain Insights; compensation for legal consultation from Parenti, Falk, Waas, Hernandez, and Cortina; Schell, Quillin, Mitchel & Cooley, LLP; Gerson Lehrman Group; Wicker, Smith, O’Hara, McCoy, Graham & Ford, PA; Conroy, Simberg, Ganon, Krevans & Abel, PA; Hershewe Law Firm, PC; and honorarium from Tarrant County Community College, American Academy of Addiction Psychiatry, Michigan State University, John Peter Smith Health Network, Medical University of South Carolina, Wayne State University, CME Inc., Temple University, and Texas Department of State Health Services. Dr Williams has received compensation for clinical work performed at the Productive Rehabilitation Institute of Dallas for Ergonomics (PRIDE) as well as his private psychology practice, Mark Williams, LLC. There are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
PY - 2008/7
Y1 - 2008/7
N2 - Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.
AB - Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.
KW - Acetylcholine
KW - Attention
KW - Cocaine dependence
KW - Executive functioning
KW - Learning and memory
KW - Reward
UR - http://www.scopus.com/inward/record.url?scp=45149123897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45149123897&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1301585
DO - 10.1038/sj.npp.1301585
M3 - Review article
C2 - 17928814
AN - SCOPUS:45149123897
SN - 0893-133X
VL - 33
SP - 1779
EP - 1797
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 8
ER -