Failure of subchronic lisuride to modify A10 dopamine autoreceptors' sensitivity

The concept that prolonged treatment with dopamine (DA) mimetics results in a subsensitivity of DA autoreceptors generally is accepted. However, the present study indicates that the administration of a rather specific DA-D2 agonist, lisuride hydrogen maleate (LIS), for one week (200 micrograms/kg/daily) failed to modify the sensitivity of DA autoreceptors of A10 neurons. Indeed, by using extracellular single unit recording in chloral hydrate-anesthetized rats, we observed that neither intravenous apomorphine nor microiontophoresis of DA changed their firing rate-depressant potency when it was estimated at 1 or 3 days after the last LIS injection. A possible interpretation of the results is that the subchronic stimulation of DA-D2 receptors activates an unknown compensatory mechanism which avoids the changes in their sensitivity. Alternatively, the possibility that LIS may also possess antagonistic properties for DA receptors, which might balance the D2 receptors activation, is discussed.