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The olivocochlear lateral efferent system (OLES) of the adult mammalian cochlea uses variety of neuroactive substances, such as acetyl choline, GABA, dopamine (DA), enkephalins, dynorphins and CGRP. These neuroactive substances have been located within the efferent, small and dense matrix, fibers and terminals of the inner spiral and tunnel bundles. However, some of these neuroactive substances have also been found outside the OLES. Acetyl choline and CGRP, for instance, appear within the olivocochlear medial efferent fibers, and DA and CGRP may also be present in the perivascular innervation. A special case is GABA innervation at the apical coil, where nerve fibers containing GABA also make synapses with OHCs bodies. All these substances of the OLES could be involved in a highly selective filter modulating the activity of primary afferent fibers. For instance, sound stimulation results in an increase of cochlear DA turnover, indicating the release of DA from OLES fibers. DA probably acts on D-2 receptors since the administration of piribedil, a D-2 agonist, results in blocking of noise effects, while D-1 receptor stimulation does not modify cochlear DA turnover induced by noise. Therefore, DA could play an important role in the modulation and noise-protection of cochlear primary afferents. During cochlear development, all the aforementioned neuroactive substances appear a long time before the onset of hearing (evidenced by the recording of cochlear compound action potential and microphonic potentials). Thus, they may act during development on the late reorganization and plasticity on the afferent and efferent fibers. Moreover, the positive neurotrophic effect observed in cultured cochlear neurons, with GABA or glutamate, add new support to that hypothesis.