Dopamine neurons: effect of lergotrile on unit activity and transmitter synthesis

Intravenous administration of increasing doses of the ergoline, lergotrile mesylate, caused a rapid, dose-dependent and haloperidol-reversible inhibition of unit activity of dopamine cells in the pars compacta of the rat substantia nigra. 6 microgram/kg caused significant depression of dopamine cell firing rates; 50% inhibition was achieved with a cumulative dose of 100 microgram/kg. 60% of the cells were completely inhibited by increasing doses of the drug, the remainder became resistant to further inhibition after reaching rates 25--50% of baseline. Pretreatment with reserpine and alpha-methylparatyrosine did not significantly attenuate the lergotrile-induced inhibition. Lergotrile had no consistent effect on firing rates of cells in the pars reticulata of the substantia nigra. The ergoline reduced the apparent activation of striatal dopamine synthesis associated with complete cessation of impulse flow in nigral-striatal dopamine neurons induced by gamma-butyrolactone treatment. These effects are compared with those of apomorphine and amphetamine. The results are consistent with the idea that lergotrile is a direct acting dopamine agonist.