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 GABAB receptor agonist l-baclofen, may be effective as a treatment. The aim of this study was to investigate the effects of early (5mg/kg s.c., 30min and then every 24h for 5days following noise exposure) and late treatment (3mg/kg/day s.c. for 4.5weeks starting at 17.5weeks 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 17.5weeks 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 5days following the acoustic trauma and also failed to reverse it when treatment was carried out every day for 4.5weeks. We also found that treatment with l-baclofen did not alter the expression of the GABAB-R2 subunit in the cochlear nucleus of noise-exposed animals.