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Vigabatrin, a GABA transaminase inhibitor, reversibly eliminates tinnitus in an animal model.
MedLine Citation:
PMID:  17221143     Owner:  NLM     Status:  MEDLINE    
Animal models have facilitated basic neuroscience research investigating the pathophysiology of tinnitus. It has been hypothesized that partial deafferentation produces a loss of tonic inhibition in the auditory system that may lead to inappropriate neuroplastic changes eventually expressed as tinnitus. The pathological down-regulation of gamma-amino butyric acid (GABA) provides a potential mechanism for this loss of inhibition. Using an animal model previously demonstrated to be sensitive to treatments that either induce or attenuate tinnitus, the present study examined the effect of the specific GABA agonist vigabatrin on chronic tinnitus. It was hypothesized that vigabatrin would decrease the evidence of tinnitus by restoring central inhibitory function through increased GABA availability. Vigabatrin has been demonstrated to elevate central GABA levels (Mattson et al. 1995). Tinnitus was induced in rats using a single 1-h unilateral exposure to band-limited noise, which preserved normal hearing in one ear. Psychophysical evidence of tinnitus was obtained using a free-operant conditioned-suppression method: Rats lever-pressed for food pellets and were trained to discriminate between the presence and absence of sound by punishing lever pressing with a mild foot shock (0.5 mA; 1 s) at the conclusion of randomly introduced silent periods (60 s) inserted into background low-level noise. Additional random insertion of pure tone and noise periods of variable intensity enabled the derivation of psychophysical functions that reflected the presence of tinnitus with features similar to 20-kHz tones. Vigabatrin was chronically administered via drinking water at 30 and 81 mg kg-1 day-1, with each dose level tested over 2 weeks, followed by a 0-mg washout test. Vigabatrin completely and reversibly eliminated the psychophysical evidence of tinnitus at both doses. Although vigabatrin has serious negative side effects that have prevented its clinical use in the USA, it is nevertheless a potentially useful tool in unraveling tinnitus pathophysiology.
Thomas J Brozoski; T Joseph D Spires; Carol A Bauer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-01-13
Journal Detail:
Title:  Journal of the Association for Research in Otolaryngology : JARO     Volume:  8     ISSN:  1525-3961     ISO Abbreviation:  J. Assoc. Res. Otolaryngol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-05     Completed Date:  2007-06-06     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  100892857     Medline TA:  J Assoc Res Otolaryngol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  105-18     Citation Subset:  IM    
Division of Otolaryngology, Southern Illinois University School of Medicine, 801 N. Rutledge St., Rm. 3205, P. O. Box 19629, Springfield, IL 62794-9629, USA.
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MeSH Terms
4-Aminobutyrate Transaminase / antagonists & inhibitors
Adaptation, Physiological
Auditory Threshold
Behavior, Animal
Disease Models, Animal
Evoked Potentials, Auditory, Brain Stem
GABA Agents / pharmacology*
Neural Inhibition / drug effects
Neuronal Plasticity / drug effects
Rats, Long-Evans
Tinnitus / drug therapy*,  physiopathology*
Vigabatrin / pharmacology*
Grant Support
Reg. No./Substance:
0/GABA Agents; 60643-86-9/Vigabatrin; EC Transaminase

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