title: Opiate dependence and withdrawal: preliminary assessment using single photon emission computerized tomography (SPECT).
abstract: Naloxone (0.8 mg, s.c.) effects on opiate withdrawal signs and symptoms and regional brain function were assessed in 10 methadone-maintained patients and 10 healthy subjects in a double-blind, placebo-controlled study. Regional brain function was assessed using single photon emission computerized tomography (SPECT) by evaluating the uptake of [99mTc]d,l-hexamethylpropyleneamine oxime (HMPAO) in the brain, a process related to regional cerebral perfusion. Comparisons of patients and healthy subjects after saline infusion suggested that chronic opiate dependence was associated with lower corrected activity ratios (regional count density/whole brain count density) in frontal and parietal cortices and greater activity ratios in the thalamus. Opiate-dependent patients, but not healthy subjects, developed opiate withdrawal signs and symptoms after naloxone administration. Following naloxone administration, patients undergoing opiate withdrawal exhibited lower whole brain count density than healthy subjects. They also had lower activity ratios in frontal and parietal cortices and increased thalamic activity ratios relative to healthy subjects receiving naloxone. Naloxone administration in healthy subjects, but not opiate withdrawal in patients, was associated with decreased right parietal cortex and increased right temporal cortex and left basal ganglia activity ratios. Relative to naloxone effects in healthy subjects, opiate withdrawal was associated with decreased whole brain count density and a reduced right temporal cortex activity ratio. This preliminary study reports an initial evaluation of HMPAO-SPECT imaging for assessing regional alterations in brain function during opiate dependence and withdrawal. While group differences were reported, the small magnitude of regional alterations in patients undergoing opiate withdrawal raised concern that HMPAO-SPECT methods employed were inadequate for assessing human regional brain function during phases of opiate addiction. Other emerging functional brain imaging technologies should be evaluated relative to improved HMPAO-SPECT methods for this purpose.
authors.affiliation: West Haven VA Medical Center, Connecticut 06516, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Krystal
authors.forename: S W
authors.initials: SW
authors.lastname: Woods
authors.forename: T R
authors.initials: TR
authors.lastname: Kosten
authors.forename: M I
authors.initials: MI
authors.lastname: Rosen
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: C C
authors.initials: CC
authors.lastname: van Dyck
authors.forename: L H
authors.initials: LH
authors.lastname: Price
authors.forename: I G
authors.initials: IG
authors.lastname: Zubal
authors.forename: P B
authors.initials: PB
authors.lastname: Hoffer
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001479:Basal Ganglia / Q000503:physiopathology; D001794:Blood Pressure; D001921:Brain / Q000000981:diagnostic imaging*; D002540:Cerebral Cortex / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000000981:diagnostic imaging* / Q000534:rehabilitation; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000000981:diagnostic imaging*; D013788:Thalamus / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D009270:Naloxone; D008691:Methadone