Baclofen reduces tone-evoked activity of cochlear nucleus neurons.
Recent evidence suggests that an excitant amino acid may be a neurotransmitter at acoustic nerve synapses in cochlear nucleus (CN). Release of excitant amino acids is reportedly reduced by baclofen, a lipophilic GABA-mimetic used to treat the spasticity of multiple sclerosis and spinal injury. Microiontophoresis of (-)baclofen suppressed spontaneous and tone-evoked activity in CN neurons. GABA inhibited the responses of most neurons responsive to (-)baclofen. However, iontophoresis of these two substances onto the same CN neuron resulted in dramatic differences in time course to maximum effect and to recovery. Onset and offset of (-)baclofen-induced firing reduction were gradual at all doses (currents), but even the highest doses rarely caused total suppression of firing. Inhibition of firing by GABA was abrupt, and total suppression was frequently observed over the range of doses used. GABA desensitization (fading) commonly occurred while the (-)baclofen response never faded. The same CN neurons were also suppressed by D-alpha-aminoadipate, which blocks certain excitatory amino acid receptors, while the GABA antagonist bicuculline had no effect on the (-)baclofen response. These findings support the hypothesis that an excitant amino acid may be a transmitter at acoustic nerve synapses in CN.
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002682:Chinchilla; D003056:Cochlear Nerve / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008144:Loudness Perception / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010898:Pitch Perception / Q000187:drug effects*; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D015074:2-Aminoadipic Acid; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline