title: Effects of early and late treatment with L-baclofen on the development and maintenance of tinnitus caused by acoustic trauma in rats.
abstract: Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Recent evidence supports the hypothesis that tinnitus is related to neuronal hyperactivity in auditory brain regions, and consequently drugs that increase GABAergic neurotransmission in the CNS, such as the GABA(B) receptor agonist L-baclofen, may be effective as a treatment. The aim of this study was to investigate the effects of early (5 mg/kg s.c., 30 min and then every 24 h for 5 days following noise exposure) and late treatment (3 mg/kg/day s.c. for 4.5 weeks starting at 17.5 weeks following noise exposure) with l-baclofen on the psychophysical attributes of tinnitus in a conditioned lick suppression model following acoustic trauma in rats. Acoustic trauma (a 16-kHz, 115-dB pure tone presented unilaterally for 1h) resulted in a significant decrease in the suppression ratio (SR) compared to sham controls in response to 20-kHz tones at 2, 10 and 17.5 weeks post-exposure (P ≤ 0.009, P ≤ 0.02 and P ≤ 0.03, respectively). However, l-baclofen failed to prevent the development of tinnitus when administered during the first 5 days following the acoustic trauma and also failed to reverse it when treatment was carried out every day for 4.5 weeks. We also found that treatment with L-baclofen did not alter the expression of the GABA(B)-R2 subunit in the cochlear nucleus of noise-exposed animals.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: McPherson
authors.affiliation: Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand. Electronic address: paul.smith@otago.ac.nz.
authors.forename: P F
authors.initials: PF
authors.lastname: Smith
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D017626:Cochlear Nucleus / Q000187:drug effects / Q000378:metabolism; D003213:Conditioning, Psychological; D016057:Evoked Potentials, Auditory, Brain Stem; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D006317:Hearing Loss, Noise-Induced / Q000150:complications* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D011601:Psychophysics; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D013997:Time Factors; D014012:Tinnitus / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
chemical_list: D058786:GABA-B Receptor Agonists; C116566:Gabbr2 protein, rat; D018080:Receptors, GABA-B; D001418:Baclofen
keywords: ABR; ANOVA; BBN; CN; CS; GABA(B) receptors; GAD-67; LMM; N-methyl-d-aspartate; NMDA; SPL; SR; acoustic trauma; analysis of variance; auditory brainstem-evoked response; broad band noise; cochlear nucleus; conditioned stimulus; glutamic-acid decarboxylase-67; l-baclofen; linear mixed model; rats; sound pressure level; suppression ratio; tinnitus