Differential effect of systemic administration of bromocriptine and L-dopa on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats

Brain Res. 1993 Apr 16;608(2):198-203. doi: 10.1016/0006-8993(93)91459-6.

Abstract

A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatment of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and L-beta-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 mumol/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 systemic application. Therapeutic as well as side effects of L-DOPA may therefore be mediated by neurochemical alterations that are more complex than previously thought.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Bromocriptine / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dialysis
  • Levodopa / pharmacology*
  • Male
  • Oxidopamine / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Bromocriptine
  • Levodopa
  • Oxidopamine
  • Acetylcholine