Ergocryptine and other ergot alkaloids stimulate the release of [H-3]dopamine from rat striatal synaptosomes

Ergocryptine is an ergot alkaloid that affects dopaminergic activity princi pally by interacting with D-2-type receptors. In this study the ability of ergocryptine and several other ergot alkaloids to release [H-3]dopamine fro m isolated nerve endings was demonstrated using in vitro superfusion of rat striatal synaptosomes. Ergocryptine, ergocristine, and bromocryptine produ ced an elevation in baseline dopamine release of approximately 400% with ef fective concentrations (EC50) of approximately 30 mu M Ergotamine, ergonovi ne, ergovaline, and ergocornine were devoid of activity. The time-course of the ergocryptine-stimulated release was relatively slow compared with amph etamine, nicotine, or K+-stimulated [H-3]dopamine release; the maximal incr ease in release required a 5-min treatment. A number of receptor antagonist s were examined for their ability to block ergocryptine-stimulated release. Of the dopaminergic, adrenergic, serotonergic, GABA-ergic, and cholinergic antagonists examined,only phentolamine produced a moderate attenuation in evoked release. Omission of Ca++ from the medium did not affect ergocryptin e-evoked release. Following ergocryptine treatment, the synaptosomes were f ully responsive to other stimulant. The results indicate that,in addition t o interacting with dopamine receptors, several ergot alkaloids may produce dopaminergic effects by increasing the release of dopamine from central. ne rve endings. Several mechanisms to account for the evoked neurotransmitter release are discussed.