This study investigates the role of dopamine, a putative lateral effer
ent neurotransmitter/modulator, in cochlear physiology and physiopatho
logy. Cochlear potentials were recorded in guinea pigs after intracoch
lear perfusion of increasing doses (0.1-1 mM) of piribedil, an agonist
of the D2/D3 receptors. A dose-dependent reduction in the amplitude o
f auditory nerve compound action potential (CAP) was observed, predomi
nantly at high-intensity tone-burst stimulations, and without signific
ant effect on CAP threshold. There was no variation of cochlear microp
honic and summating potential. When 1 mM piribedil was perfused into t
he cochlea during continuous 130 dB SPL pure tone exposure (6 kHz, 15
min), CAP threshold shifts were significantly less than in control ani
mals with artificial perilymph-perfused cochleas. No dendritic damage
was observed, although there was evident hair cell damage. Similarly,
radial dendrites were clearly protected against ischemia-induced damag
e when 1 mM piribedil was applied prior to a 10-min ischemia. These re
sults suggest that dopamine modulates the activity of radial afferent
fibers via D2/D3 receptors. The protective effect of piribedil during
acoustic trauma or ischemia suggests that this modulation corresponds
to a prevention of excitotoxicity due to dysfunction of inner hair cel
l neurotransmission.