differential effect of systemic administration of bromocriptine and l-DOPA on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats

A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatments of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and l-β-3-,4-dihydroxyphenylalanine (l-DOPA), on the release of striatal acetylcholine (ACh) in intact and 6-hydroxy-dopamine-treated rats using in vivo microdialysis. Lesioned rats with a 90% tissue depletion of striatal dopamine (DA) had a significantly higher output of striatal ACh than unlesioned rats (88 fmol/min vs. 52 fmol/min; 0.3 μmol/l neostigmine in perfusate). BROMO (4 mg/kg) inhibited the output of striatal ACh in both groups. Whereas the lowest dose of l-DOPA (50 mg/kg) potently stimulated ACh output in lesioned rats, unlesioned rats were significantly less responsive. A higher dose of l-DOPA (100 mg/kg) stimulated ACh output to the same extent in both groups. At the highest dose tested, l-DOPA (200 mg/kg) given to intact rats did not further increase striatal ACh output. Thus, BROMO decreases whereas l-DOPA increases striatal ACh release after systematic application. Therapeutic as well as side effects of l-DOPA may therefore be mediated by neurochemical alterations that are more complex than previously thought.