l-DOPA and psychosis: Evidence for l-DOPA-induced increases in prefrontal cortex dopamine and in serum corticosterone

• Published in: Biological psychiatry (1969) 1995-11, Vol.38 (10), p.669-676
• Main Authors: Carey, Robert J., Pinheiro-Carrera, Marinete, Dai, Huiliang, Tomaz, Carlos, Huston, Joseph P.
• Format: Article
• Language: English
• Subjects: Animals; Antiparkinson Agents - pharmacology; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corticosterone - blood; dopamine; Dopamine - metabolism; Drug toxicity and drugs side effects treatment; Homovanillic Acid - metabolism; Levodopa - blood; Levodopa - pharmacology; Male; Medical sciences; Parkinson's disease; Pharmacology. Drug treatments; prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Psychoses, Substance-Induced - metabolism; Psychosis; Rats; Rats, Sprague-Dawley; Regression Analysis; Risk Factors; serotonin; Toxicity: nervous system and muscle
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/0006-3223(94)00378-5

l-DOPA can often induce psychotic reactions during treatment for Parkinson's disease. This study was undertaken to assess, in an animal model of Parkinson's disease, the impact of l-DOPA treatment on two potential biological risk factors for psychosis, namely, an increase in prefrontal cortex dopamine and an increase in the stress-related hormone corticosterone. Hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA) lesions which resulted in severe unilateral denervation of dopamine neurons were treated with either saline or 25 mg/kg l-DOPA methyl 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 metabolite homovanillic acid Serum l-DOPA, however, was found not to be correlated with serum or brain concentrations of serotonin, 5-hydroxyindoleacetic acid, or norepinephrine. These findings support the possibility that chronic l-DOPA treatment can expose parkinsonian patients to two significant risk factors for psychosis: 1) increased levels of prefrontal cortex dopamine, and 2) increased levels of serum corticosterone.