title: Altered neural cholinergic receptor systems in cocaine-addicted subjects.
abstract: 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 (p<0.005) 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.
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-8564, USA. bryon.adinoff@utsouthwestern.edu
authors.forename: Bryon
authors.initials: B
authors.lastname: Adinoff
authors.forename: Michael D
authors.initials: MD
authors.lastname: Devous
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Williams
authors.forename: Susan E
authors.initials: SE
authors.lastname: Best
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harris
authors.forename: Abu
authors.initials: A
authors.lastname: Minhajuddin
authors.forename: Tanya
authors.initials: T
authors.lastname: Zielinski
authors.forename: Munro
authors.initials: M
authors.lastname: Cullum
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging* / Q000187:drug effects; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage; D011569:Psychiatric Status Rating Scales; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012601:Scopolamine / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D010830:Physostigmine; D012601:Scopolamine
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