Effect of lergotrile on3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain

Abstract

Lergotrile, a dopamine agonist, lowered whole brain DOPAC (3, 4-dihydroxyphenylacetic acid) concentration in rats. At low doses down to 0.5 mg/kg of lergotrile mesylate, this effect occurred within 30 min, whereas at higher doses (20 mg/kg) the decline in DOPAC was delayed. The decrease in DOPAC persisted for several hours and presumably resulted from a compensatory decrease in brain dopamine turnover secondary to receptor stimulation by lergotrile. Other indications of decreased brain dopamine turnover after lergotrile included (a) a slower decline in dopamine concentration after synthesis inhibition byα-methyltyrosine, (b) a slower declineα-methyl-m-tyramine, a false transmitter that is stored and released by dopamine neurons, and (c) a decreased accumulation of dopamine in response toγ-butyrolactone, an agent that blocks firing and dopamine release by dopamine neurons. Lergotrile mesylate (20 mg/kg) also increased brain levels of 5-hydroxyindoleacetic acid and of 3-methoxy-4-hydroxyphenylethylene glycol sulfate, metabolites of serotonin and norepinephrine, respectively, and these increases were not antagonized by spiperone, a dopamine receptor antagonist.