Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with high-dose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and ;self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding and morphine-reinforced behavior, and these effects may be mediated by psychostimulant metabolites.

OBJECTIVE: The authors' goal was to test the efficacy of selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who had negative symptoms of moderate or greater severity. METHOD: A 12-week, double-blind, placebo-controlled, multicenter trial of oral selegiline augmentation of antipsychotic medication was carried out. Outpatients were chosen who did not manifest severe positive symptoms at baseline, who did not meet criteria for coexisting major depression, and who had been maintained on a stable regimen of antipsychotic medication. RESULTS: Negative symptoms were found to be significantly more improved in the patients who received selegiline, and global improvement scores reinforced the impression that selegiline augmentation was beneficial. CONCLUSIONS: These findings support further investigation of low-dose selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who have at least a moderate burden of negative symptoms.

OBJECTIVES: The aim of this study was to examine the selegiline treatment compared to methylphenidate (MPH) in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHOD: Forty subjects, aged 6-15 years, boys and girls, who were diagnosed as having ADHD, using the criteria of the Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV), were randomly assigned to receive either selegiline or MPH for 60 days. Treatment outcomes were assessed using the Attention Deficit Hyperactivity Scale (ADHS) administered at baseline and on days 14, 28, 42, and 60 following the commencement of treatment. Side effects were also rated. RESULTS: There were no significant differences between sex, age, weight, and ethnicity of participants in the 2 groups. Both groups showed a significant improvement over the 60 days of treatment resulting from the teachers' and parents' ADHS scores across the treatment. CONCLUSION: Following the trial, MPH did not effect greater mean improvement as a result of the parents' or teachers' ADHS scores than selegiline. Thus, selegiline appears to be effective and well tolerated for ADHD in children and adolescents.