ELEVATED STRIATAL DOPAMINE LEVELS FOLLOWING ADMINISTRATION OF D-DOPA AND ITS ALPHA-KETO ACID METABOLITE DHPPA - BEHAVIORAL AND PHYSIOLOGICAL-STUDIES IN-VIVO IN THE RAT

The D stereoisomer of dihydroxyphenylalanine (D-DOPA) and its alpha-ke to acid metabolite 3,4-dihydroxyphenylpyruvic acid (DHPPA), when infus ed into the striatum, significantly increased in vivo extracellular do pamine levels. Following D-DOPA administration, the cumulative increas e in dopamine levels was 30% of the increase following L-DOPA; followi ng DHPPA it was 11% that of L-DOPA. Rats with unilateral 6-hydroxydopa mine-induced lesions of the substantia ni,ora demonstrated brisk contr alateral turning following each compound. The turning, however, was de layed by 10-20 min and total turning was 40% less following D-DOPA and 57% less following DHPPA than it was following L-DOPA. These data ind icate that exogenously administered D-DOPA can be metabolized in vivo within the brain to dopamine and suggest this may occur via a transami nation pathway in which DHPPA is an intermediary metabolite. The possi ble relevance of these findings to the treatment of Parkinson's diseas e is discussed.