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 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.
Vibert
N
N
Département de Physiologie, CMU, Geneva, Switzerland.
Serafin
M
M
Crambes
O
O
Vidal
P P
PP
Mühlethaler
M
M
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010891:Piribedil / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D017661:Receptors, Presynaptic / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014726:Vestibular Nuclei / Q000166:cytology* / Q000187:drug effects*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017661:Receptors, Presynaptic; D013779:Tetrodotoxin; D010891:Piribedil; D002118:Calcium; D004298:Dopamine; D001640:Bicuculline