TY - JOUR
T1 - Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria
AU - Bartzokis, George
AU - Beckson, Mace
AU - Newton, Thomas
AU - Mandelkern, Mark
AU - Mintz, Jim
AU - Foster, Jennifer A.
AU - Ling, Walter
AU - Bridge, T. Peter
N1 - Funding Information:
This work was supported by the Medication Development Division of the National Institute on Drug Abuse (1YO1 DA 50038), the Research and Psychiatry Services of the Department of Veterans Affairs, the Marie Wilson Howells Endowment and by Pharmavene Inc., Gaithersburg, Maryland, who provided matched placebo and selegiline tablets. The authors thank Edythe D. London, Ph.D. of the NIDA Brain Imaging Center for consultations in designing the protocol and reviewing the manuscript; Nora Volkow, M.D. of the Brookhaven National Laboratory for consultations in designing the protocol; Charles Brown, M.D. for performing the PET scans; Horst Meissner, M.D., Michael Goldman, M.D., Sc.D., and Jill Tureaud, R.N. for medical screening and monitoring cocaine infusion; Judith Lindholm, M.S. for coordinating infusions and recruitment; and Marguerite Callinan, M.A. for coordinating the imaging sessions.
PY - 1999/6
Y1 - 1999/6
N2 - To test the effect of selegiline, a specific monoamine oxidase-B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ('high') produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1,21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1,20, p = .012). The concomitant changes in both the subjective experience of the 'high' and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence. Copyright (C) 1999 American College of Neuropsychopharmacology.
AB - To test the effect of selegiline, a specific monoamine oxidase-B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ('high') produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1,21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1,20, p = .012). The concomitant changes in both the subjective experience of the 'high' and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence. Copyright (C) 1999 American College of Neuropsychopharmacology.
KW - Amygdala
KW - Cocaine
KW - Euphoria
KW - Hippocampus
KW - MRI
KW - PET
KW - Selegiline
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U2 - 10.1016/S0893-133X(98)00092-X
DO - 10.1016/S0893-133X(98)00092-X
M3 - Article
C2 - 10327427
AN - SCOPUS:0033151283
VL - 20
SP - 582
EP - 590
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 6
ER -