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Preliminary Data evaluating the Effect of Gabapentin on Auditory Temporal Resolution characterized by a Gap Detection Task in Gerbils. (Abstract of ARO Meeting Denver, Colorado) Otto Gleich, Juergen-Theodor Fraenzer, Jürgen Strutz University of Regensburg

Impaired auditory temporal processing is improved by the drug γ-vinyl-GABA (Sabril) that increases GABA levels in the brain (Gleich et al., 2003, Neuroreport 14:1877-1880). However, Sabril can reduce the visual field. Thus we began evaluating the anticonvulsant Gabapentin (GP). GP was effective in the treatment of certain forms of tinnitus, where GABA mechanisms have repeatedly been implicated (Bauer and Brozoski, 2001, JARO 2:54-64; 2006, Laryngoscope 116: 675-681). In each animal threshold for an 800 ms broad band noise pulse was determined. The noise pulse was subsequently used as a carrier for the gap with a level set 30 dB above each individual’s threshold. GP was administered in the drinking water at a dose of 350 mg/kg/day. Testing was performed 1-2 hours after GP intake. Gap detection thresholds were determined, before, during and at least two weeks after cessation of GP administration for 5 young (8-13 months) and 10 old (27-37 months) gerbils. A two way repeated measure ANOVA using age and treatment as factors revealed a significantly higher mean gap detection threshold for old (3.1 ms) as compared to young (2.0 ms) gerbils (p = 0.019). Mean gap detection threshold during GP treatment (2.9 ms) was slightly higher compared to thresholds deter- mined before (2.5 ms) and after GP treatment (2.3 ms), however, these differences were not significant (p = 0.212) and there was no interaction between age and treatment (p = 0.923). These preliminary data provide no evidence for a beneficial effect of GP on temporal resolution, if anything, the group mean data suggest that performance may deteriorate during GP treatment. In con- trast to initial expectations, GP has no effect on GABA receptors, enzymes or transporters (Errington et al., 2005, Curr. Top. Med. Chem. 5, 15-30) and consequently cannot compensate age dependent declines in the GABA system (We thank S. Kopetschek and C. Wögerbauer for help with the behavioral experiments. Supported by the DFG Str275/4-5).

Sulpiride plus hydroxyzine decrease tinnitus perception. Auris Nasus Larynx. 2007 Mar;34(1):23-7. Epub 2006 Nov 21. Lopez-Gonzalez MA, Moliner-Peiro F, Alfaro-Garcia J, Esteban-Ortega F Otorhinolaryngology Department, Virgen del Rocio University Hospital, Seville, Spain. malopez@cica.es

Objectives: The aim of the study is to confirm the effectiveness of sulpiride and hydroxyzine in tinnitus patients. The administration of sulpiride, a D2 antagonist of dopamine receptors, together with hydroxyzi- ne, a subcortical sedative, covers the areas of tinnitus perception. Methods: A prospective, randomized, single blinded, placebo-control study was done in general oto- rhinolaryngology consultations for 2002-2004 in Seville and Zaragoza (Spain). One hundred and fifty patients consulted for subjective tinnitus. They were included randomly in three groups of 50. A group took sulpiride (50 mg/8 h) alone, other the same dose of sulpiride plus hydroxyzine (25 mg/12 h), and the third placebo (lactose), for 1 month. One hundred and twenty-two patients completed the study. Clinical history, tonal audiometry, tympanometry, and tinnitometry were done in the beginning and end of the study. Subjective Grading of Tinnitus Perception and visual analogical scale (0-10) were done for result evaluation. Results: Based on the Subjective Grading of Tinnitus Perception, tinnitus perception diminished by 56% in patients treated with sulpiride and by 81% in patients treated with sulpiride plus hydroxyzine. Based on the visual analogical scale, tinnitus perception diminished from 7.8 to 6.3 in the patients treated with sulpiride, and from 7.8 to 5.1 in those treated with sulpiride plus hydroxyzine. Conclusions: Sulpiride plus hydroxyzine decreases tinnitus perception. Tinnitus auditolimbic dopamin- ergic pathway opens wide therapeutical implications.

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