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Selegiline effects on
cocaine-induced changes
in medial temporal lobe metabolism and subjective
ratings of euphoria
Bartzokis G, Beckson M, Newton T, Mandelkern M,
Mintz J, Foster JA, Ling W, Bridge TP
Psychiatry Service
Little Rock VA Medical Center AR 72114, USA.
Neuropsychopharmacology 1999 Jun; 20(6):582-90
ABSTRACT
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.
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