Agonist and antagonist actions of lisuride on dopamine neurons: electrophysiological evidence

The effect of lisuride (LIS) on the firing rate of A9 dopamine (DA) neurons in chloral-hydrate anesthetized and unanesthetized (paralyzed) rats was compared. In both preparations, the microiontophoretic application of LIS onto DA cell bodies consistently inhibited the electrical activity of the neurons. On the other hand, the effect of intravenous LIS differed in the two preparations. In anesthetized rats LIS (10-100 micrograms/kg) inhibited in a dose-related manner the firing rate of most DA neurons tested, whereas in unanesthetized rats LIS produced a dose-related increase in firing rate. The latter effect was transient, subsiding within 5 min, and was followed by the return of firing rate to baseline or slightly below it. Irrespective of the animal preparation, after the initial effect of LIS had subsided, DA neurons became totally insensitive to additional doses of LIS, to apomorphine and haloperidol. Such an insensitivity of DA neurons was present 1 to 6 but not 24 h after LIS (0.2 mg/kg, subcutaneously) treatment. A hypothesis is proposed to explain the different effects of LIS.