Selegiline effects on cocaine-induced changes in medial temporal lobe
metabolism and subjective ratings of euphoria
by
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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