Dopaminergic Agonists Have Both Presynaptic and Postsynaptic Effects on the Guinea-pig's Medial Vestibular Nucleus Neurons

A number of studies have indicated a possible interaction between dopamine and the vestibular system. Using intracellular recordings in brainstem slices, we have tested the effects of dopamine and other dopaminergic compounds on guinea‐pig medial vestibular nucleus (MVN) neurons. In normal medium, MVN neurons were depolarized by dopamine as well as by (‐)quinpirole and piribedil, which are selective D2 dopaminergic agonists. The dependence of this effect on the presence of D2 receptors was confirmed by using (‐)sulpiride, a D2 antagonist which blocked the depolarizing effect of dopamine. Dopaminergic D1 receptors were apparently not involved in this effect since a selective D1 agonist, SKF‐38393, had no effect on MVN neurons and the D1 antagonist (+) SCH‐23390 could not block the effect of dopamine. These depolarizing responses to dopamine must be due to a presynaptic action on terminals that normally release GABA spontaneously on MVN neurons, and tonically maintain them in a state of hyperpolarization. Indeed, such a spontaneous release was demonstrated to occur in the slice since application of bicuculline, a GABAA antagonist, depolarized MVNneurons in normal saline, but not in a high Mg2+/low Ca2+ solution known to block synaptic transmission. When dopamine was applied in conditions in which no GABAA‐dependent transmission could occur (either in the presence of bicuculline or in a high Mg2+/low Ca2+ solution) only a hyperpolarizing, most probably postsynaptic, effect occurred. These results indicate that dopamine might exert in vivo a significant modulatory action on the vestibular system, either by a direct action on the vestibular neurons or by modulation of GABAergic transmission.