L-DOPA AND PSYCHOSIS - EVIDENCE FOR L-DOPA-INDUCED INCREASES IN PREFRONTAL CORTEX DOPAMINE AND IN SERUM CORTICOSTERONE

L-DOPA can often induce psychotic reactions during treatment for Parki nson's disease. This study was undertaken to assess, in an animal mode l of Parkinson's disease, the impact of L-DOPA treatment on two potent ial biological risk factors for psychosis, namely, an increase in pref rontal cortex dopamine and an increase in the stress-related hormone c orticosterone. Hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA) lesions which resulted in severe unilateral denervation of d opamine neurons were treated with either saline or 25 mg/kg L-DOPA met hyl ester (with 2 mg/kg) carbidopa). Serum L-DOPA concentrations were found to be positively and highly correlated with serum corticosterone , with medial prefrontal cortex dopamine and with the dopamine metabol ite homovanillic acid. Serum L-DOPA however, was found not to be corre lated with serum or brain concentrations of serotonin, 5-hydroxyindole acetic acid acid, or norepinephrine. These findings support the possib ility that chronic L-DOPA treatment can expose parkinsonian patients t o two significant risk factors fro psychosis: 1) increased levels of p refrontal cortex dopamine, and 2) increased levels of serum corticoste rone.