Dopaminergic agonists have both presynaptic and postsynaptic effects on the guinea-pig's medial vestibular nucleus...

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 MVN neurons 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.