Electrophysiological evaluation of a partial agonist of dopamine receptors.

The ergot derivative trans-dihydrolisuride (TDHL) was tested for its effects on firing rates of dopaminergic (DA) neurons located in the substantia nigra pars compacta of chloral hydrate-anesthetized rats. Using extracellular single-barreled microelectrodes, DA neurons were identified by their long duration, positive-negative action potentials and their slow bursting pattern of spontaneous firing, as well as by the location of recording sites through histological recoveries of dye deposits. Like haloperidol and clozapine, which are full DA receptor antagonists, TDHL antagonized the depression in DA neuron firing induced by systemic amphetamine. However, where full antagonists completely reversed the amphetamine effect, TDHL could do so only partially, the maximal effect being around half. Like DA agonists, but unlike DA antagonists, TDHL also depressed the spontaneous firing rates of DA neurons. But whereas the full agonist apomorphine completely inhibited firing of DA neurons, TDHL only depressed firing rates by about half, even at high doses. These data support the contention that TDHL is a partial DA agonist.