TY - JOUR
T1 - Altered neural cholinergic receptor systems in cocaine-addicted subjects
AU - Adinoff, Bryon
AU - Devous, Michael D.
AU - Williams, Mark J.
AU - Best, Susan E.
AU - Harris, Thomas S.
AU - Minhajuddin, Abu
AU - Zielinski, Tanya
AU - Cullum, Munro
N1 - Funding Information:
Bryon Adinoff has received grant/research support from the NIAAA, NIDA, Department of Veterans Affairs. He has served as Consultant: Pain Insights, medical malpractice consultant to Conroy, Simberg, Ganon, Krevans & Abel, PA; as advisor to GlaxoSmithKline; as legal consultant to The Hershewe Law Firm, PC; and has received Honoraria: CME, from the Temple University, Texas, Department of State Health Services in 2006. He has served as legal consultant to Phillips Lytle LLP for GSK; as advisor to GlaxoSmithKline; as medical malpractice consultant to The Hershewe Law Firm, PC; and has received Honoraria: from American Academy of Addiction Psychiatry, Medical University of South Carolina in 2007. He also served as medical malpractice consultant to Simon Pissante PC; as advisor to Teva Pharmaceutical Industries; as medical malpractice consultant to Shook, Hardy & Bacon LLP for tobacco companies; and has received Honoraria: from American Academy of Addiction Psychiatry, University of New Mexico in 2008. Michael D Devous has served on the Scientific Advisory Board of AVID Radiopharmaceuticals and also received research support from AVID Radiopharmaceuticals and Alseres. The remaining authors declare no conflict of interest.
Funding Information:
We thank the staff of the Substance Abuse Team at the VA North Texas Health Care System, Homeward Bound, and the Nexus Recovery Center for their support in the screening and recruitment of study subjects. Dr Adinoff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was funded by NIH DA11434 and supported by the VA North Texas Health Care System. Ceretec (HMPAO) was generously supplied by GE Healthcare.
PY - 2010/6
Y1 - 2010/6
N2 - Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1-to 6-week abstinent, cocaine-(and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.
AB - Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1-to 6-week abstinent, cocaine-(and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.
KW - Acetylcholine
KW - Addiction and substance abuse
KW - Biological psychiatry
KW - Clinical or preclinical
KW - Cocaine addiction
KW - Imaging
UR - http://www.scopus.com/inward/record.url?scp=77952426519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952426519&partnerID=8YFLogxK
U2 - 10.1038/npp.2010.18
DO - 10.1038/npp.2010.18
M3 - Article
C2 - 20393457
AN - SCOPUS:77952426519
SN - 0893-133X
VL - 35
SP - 1485
EP - 1499
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 7
ER -