Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria.
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.
D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D005059:Euphoria / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed