Effects of a dopaminergic agonist in the guinea pig cochlea.
This study investigates the role of dopamine, a putative lateral efferent neurotransmitter/modulator, in cochlear physiology and physiopathology. Cochlear potentials were recorded in guinea pigs after intracochlear perfusion of increasing doses (0.1-1 mM) of piribedil, an agonist of the D2/D3 receptors. A dose-dependent reduction in the amplitude of auditory nerve compound action potential (CAP) was observed, predominantly at high-intensity tone-burst stimulations, and without significant effect on CAP threshold. There was no variation of cochlear microphonic and summating potential. When 1 mM piribedil was perfused into the cochlea during continuous 130 dB SPL pure tone exposure (6 kHz, 15 min), CAP threshold shifts were significantly less than in control animals 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 damage when 1 mM piribedil was applied prior to a 10-min ischemia. These results 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 cell neurotransmission.
d'Aldin
C
C
INSERM (U254), Laboratoire de Neurobiologie de l'Audition et Plasticité Synaptique, CHU Hôpital St. Charles, Montpellier, France.
Puel
J L
JL
Leducq
R
R
Crambes
O
O
Eybalin
M
M
Pujol
R
R
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D007511:Ischemia / Q000503:physiopathology; D008854:Microscopy, Electron; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009847:Olivary Nucleus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009925:Organ of Corti / Q000187:drug effects / Q000648:ultrastructure; D010891:Piribedil / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects
D000978:Antiparkinson Agents; D017448:Receptors, Dopamine D2; D010891:Piribedil; D004298:Dopamine