A dose–response analysis of the effects of L-baclofen on chronic tinnitus caused by acoustic trauma in rats

Glutamic acid decarboxylase levels in the cochlear nucleus of rats with acoustic trauma-induced chronic tinnitus

“…A significant reduction in GAD65 expression was also reported in the AC at 7-15 days after acoustic trauma, which was correlated with a reduction of inhibitory synaptic transmission in the high frequency area that matches the tinnitus pitch in the same animals [16]. The chronic decrease in GABAergic activity beyond the CN may have significant implications and studies based on pharmacological intervention have shown that GABA has an integral role in the chronicity of tinnitus through the auditory pathways [12,19,20]. Therefore, the lack of long-term changes in GAD levels observed in this study is generally consistent with the reported temporal nature of GAD changes in the CN following acoustic trauma and suggests that once tinnitus is established, decreases in GAD levels in the CN may not be necessary for the continuation of tinnitus.…”

“…One of the hypotheses is that a down-regulation of inhibitory neurotransmission might be responsible for the neuronal hyperactivity and tinnitus generation [13,15]. This was supported by evidence that pharmacological manipulations enhancing brain GABAergic transmission reduced behavioural signs of tinnitus in animals [6,16,20]. It has been shown that a hearing loss-induced decrease in inhibitory synaptic transmission occurs in the auditory cortical area corresponding to the tinnitus frequency and this decrease in inhibitory synaptic transmission is also correlated with a reduced level of glutamic acid decarboxylase (GAD), the enzyme responsible for the synthesis of GABA, in the same area [16].…”

The anti-inflammatory selective melanocortin receptor subtype 4 agonist, RO27-3225, fails to prevent acoustic trauma-induced tinnitus in rats

“…Unilateral noise trauma was delivered using a procedure described by Bauer and colleagues and in our own publications (Bauer and Brozoski, 2001;Brozoski et al, 2007;Zheng et al, 2011aZheng et al, , 2011bZheng et al, , 2011cZheng et al, , 2012aZheng et al, , 2012b. Briefly, the animals were anaesthetised with a fentanyl (0.2 mg/kg, s.c.) and medetomidine hydrochloride (0.5 mg/ kg, s.c.) mixture and placed in a modified stereotaxic head frame inside a sound attenuation chamber.…”

“…The 1/4-inch microphone was placed in the chamber during the noise exposure to ensure that the sound field was effectively contained by the inserted speculum. The sham animals received the same anaesthetics and were kept under anaesthesia for the same duration as the noise trauma animals, but without noise exposure (Zheng et al, 2011a(Zheng et al, , 2011b(Zheng et al, , 2011c(Zheng et al, , 2012a(Zheng et al, , 2012b.…”

“…Tone bursts (2 ms rise/decay, 1 ms plateau) were presented in a decreasing intensity series, beginning with levels that elicited distinct evoked potentials. Hearing thresholds were indicated by the lowest intensity that produced visually distinct potentials, progressing in 20-, 10-, and 5 dB steps (Zheng et al, 2011a(Zheng et al, , 2011b(Zheng et al, , 2011c(Zheng et al, , 2012a(Zheng et al, , 2012b.…”