Increase in cochlear microphonic potential after toluene administration.
Human and animal studies have shown that toluene can cause hearing loss. In the rat, the outer hair cells are first disrupted by the ototoxicant. Because of their particular sensitivity to toluene, the cochlear microphonic potential (CMP) was used for monitoring the cochlea activity of anesthetized rats exposed to both noise (band noise centered at 4 kHz) and toluene. In the present experiment, the conditions were specifically designed to study the toluene effects on CMP and not those of its metabolites. To this end, 100-microL injections of a vehicle containing different concentrations of solvent were made into the carotid artery connected to the tested cochlea. Interestingly, an injection of 116.2-mM toluene dramatically increased in the CMP amplitude (approximately 4 dB) in response to an 85-dB SPL noise. Moreover, the rise in CMP magnitude was intensity dependent at this concentration suggesting that toluene could inhibit the auditory efferent system involved in the inner-ear or/and middle-ear acoustic reflexes. Because acetylcholine is the neurotransmitter mediated by the auditory efferent bundles, injections of antagonists of cholinergic receptors (AchRs) such as atropine, 4-diphenylacetoxy-N-methylpiperidine-methiodide (mAchR antagonist) and dihydro-beta-erythroidine (nAchR antagonist) were also tested in this investigation. They all provoked rises in CMP having amplitudes as large as those obtained with toluene. The results showed for the first time in an in vivo study that toluene mimics the effects of AchR antagonists. It is likely that toluene might modify the response of protective acoustic reflexes.
Lataye
Robert
R
Laboratoire de Neurotoxicité, Institut National de Recherche et de Sécurité, Avenue de Bourgogne, BP 27 Vandoeuvre, 54501 Cedex, France.
Maguin
Katy
K
Campo
Pierre
P
D000161:Acoustic Stimulation; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000633:toxicity; D009476:Neurons, Efferent / Q000187:drug effects / Q000378:metabolism; D009622:Noise; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D012022:Reflex, Acoustic / Q000187:drug effects; D012997:Solvents / Q000633:toxicity*; D014050:Toluene / Q000633:toxicity*
D018680:Cholinergic Antagonists; D005839:Gentamicins; D010880:Piperidines; D011950:Receptors, Cholinergic; D012997:Solvents; D004079:Dihydro-beta-Erythroidine; D014050:Toluene; C004873:beta-erythroidine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium