Cannabinoid receptor down-regulation in the ventral cochlear nucleus in a salicylate model of tinnitus

Zheng, Yiwen; Baek, Jean-Ha; Smith, Paul F.; Darlington, Cynthia L.

doi:10.1016/j.heares.2007.01.028

Cited by 45 publications

(53 citation statements)

References 20 publications

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“…Combined with previous reports about changes in DR [5] and CR [6] activities and/or functions, we suggested that a high dose of salicylate could not only induce tinnitus but also modulate expression of DR and/or CR at the genetic level and beyond in mice.…”

Section: Discussionsupporting

confidence: 83%

“…For example, tinnitus was associated with increased activity or function of N-methyl- D -aspartate receptor (NR) in the inner ear [2], vanilloid receptor in the inner ear [3], acetylcholine receptor in the auditory cortex [4], and dopamine receptor (DR) in the auditolimbic dopaminergic pathway [5]. In contrast, decreased activity or function of cannabinoid receptor (CR) in the ventral cochlear nucleus [6] and γ-aminobutyric acid receptor (GABA receptor, GR) in the inferior colliculus (IC) [7] or auditory cortex [8] was found during the tinnitus condition. Recently, inflammation [9,10,11] and/or oxidative stress [12] were hypothesized as novel mechanisms for tinnitus.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Dopamine Receptor 1A and Cannabinoid Receptor 1 Genes in the Cochlea and Brain after Salicylate-Induced Tinnitus

Hwang

Chan

2016

ORL

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The purpose of this study was to investigate the mRNA expression of the dopamine receptor 1A (DR1A) and cannabinoid receptor 1 (CR1) genes in mice with tinnitus. Sixteen 3-month-old male SAMP8 mice were randomly and equally divided into two groups (8 mice in each group): a control (saline-treated) group and a tinnitus (salicylate-treated) group. The mRNA expression of the DR1A and CR1 genes in the cochleae and brains of the mice was evaluated after tinnitus had been induced by intraperitoneal injection of sodium salicylate (300 mg/kg body weight). The results showed that 4-day salicylate treatment (unlike 4-day saline treatment) caused a significant increase in the tinnitus score and in mRNA expression of the DR1A gene in the cochlea, the brainstem and inferior colliculus, the hippocampus and parahippocampus, and the temporal lobe, but not the frontal lobe. Conversely, 4-day salicylate treatment caused significantly lower mRNA expression of the CR1 gene in the cochlea and all the brain areas tested. In summary, salicylate-induced tinnitus may be associated with increased mRNA expression of the DR1A gene - but with decreased mRNA expression of the CR1 gene - in the cochlea and in many tinnitus-related brain areas.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Expression of Dopamine Receptor 1A and Cannabinoid Receptor 1 Genes in the Cochlea and Brain after Salicylate-Induced Tinnitus

Hwang

Chan

2016

ORL

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“…In light of several studies suggesting increased spontaneous activity in DCN cells in animal models of tinnitus (Brozoski et al 2002;Kaltenbach and Afman 2000;Kaltenbach et al 1998Kaltenbach et al , 2004Kaltenbach et al , 2005, a novel hypothesis proposes that activity-dependent mechanisms that change the balance of excitation and inhibition on fusiform cells could lead to hyperactivity of fusiform cells via plasticity-like mechanisms (Tzounopoulos 2008). Consistent with this hypothesis, recent studies showed that CB1Rs are downregulated in the cochlear nucleus in an animal model of tinnitus (Zheng et al 2007). Therefore determining the functional role of EC signaling in determining the output of the DCN may also lead to a better understanding on the cellular mechanisms underlying tinnitus.…”

Section: Ec Signaling Synaptic Plasticity and Tinnitusmentioning

confidence: 90%

Distinct Functional and Anatomical Architecture of the Endocannabinoid System in the Auditory Brainstem

Zhao

Rubio²,

Tzounopoulos³

2009

Journal of Neurophysiology

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Zhao Y, Rubio ME, Tzounopoulos T. Distinct functional and anatomical architecture of the endocannabinoid system in the auditory brainstem. J Neurophysiol 101: 2434 -2446, 2009. First published March 11, 2009 doi:10.1152/jn.00047.2009. Endocannabinoids (ECs) act as retrograde messengers that enable postsynaptic cells to regulate the strength of their synaptic inputs. Here, by using physiological and histological techniques, we showed that, unlike in other parts of the brain, excitatory inputs are more sensitive than inhibitory inputs to EC signaling in the dorsal cochlear nucleus (DCN), an auditory brainstem nucleus. The principal cells of the DCN, fusiform cells, integrate acoustic signals through nonplastic synapses located in the deep layer with multimodal sensory signals carried by plastic parallel fibers in the molecular layer. Parallel fibers contact fusiform cells and inhibitory interneurons, the cartwheel cells, which in turn inhibit fusiform cells. Postsynaptic depolarization or pairing of postsynaptic potentials (PSPs) with action potentials (APs) induced EC-mediated modulation of excitatory inputs but did not affect inhibitory inputs. Quantitative electron microscopical studies showed that glutamatergic terminals express more cannabinoid 1 receptors (CB1Rs) than glycinergic terminals. Fusiform and cartwheel cells express diacylglycerol lipase ␣ and ␤ (DGL␣/␤), the two enzymes involved in the generation of the EC, 2-arachidonoyl-glycerol (2-AG). DGL␣ and DGL␤ are found in the spines of cartwheel but not fusiform cells indicating that the synthesis of ECs is more distant from parallel fiber synapses in fusiform than cartwheel cells. The differential localization and density of DGL␣/␤ and CB1Rs leads to cell-and input-specific EC signaling that favors activitydependent EC-mediated suppression at synapses between parallel fibers and cartwheel cell spines, thus leading to reduced feedforward inhibition in fusiform cells. We propose that EC signaling is a major modulator of the balance of excitation and inhibition in auditory circuits.

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“…Both CB 1 and CB 2 receptors have been identified in the cochlear nucleus (Baek et al, 2008;Gong et al, 2006;Tzounopoulos et al, 2007;Zhao et al, 2009;Zheng et al, 2007), and recent electrophysiological studies indicate that these CB 1 receptors are functional and contribute to the regulation of longterm depression (LTD) (Tzounopoulos et al, 2007;Zhao et al, 2009). In the only study to date of CB 1 receptors in relation to tinnitus, Zheng et al (2007) reported that CB 1 receptors were down-regulated in the ventral, but not the dorsal, cochlear nucleus in the salicylate animal model of tinnitus. Therefore, it is conceivable that CB 1 and CB 2 cannabinoid receptors may contribute to the pathophysiology of tinnitus.…”

Section: Introductionmentioning

confidence: 99%

The effects of the synthetic cannabinoid receptor agonists, WIN55,212-2 and CP55,940, on salicylate-induced tinnitus in rats

et al. 2010

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Cannabinoid receptor down-regulation in the ventral cochlear nucleus in a salicylate model of tinnitus

Cited by 45 publications

References 20 publications

Expression of Dopamine Receptor 1A and Cannabinoid Receptor 1 Genes in the Cochlea and Brain after Salicylate-Induced Tinnitus

Expression of Dopamine Receptor 1A and Cannabinoid Receptor 1 Genes in the Cochlea and Brain after Salicylate-Induced Tinnitus

Distinct Functional and Anatomical Architecture of the Endocannabinoid System in the Auditory Brainstem

The effects of the synthetic cannabinoid receptor agonists, WIN55,212-2 and CP55,940, on salicylate-induced tinnitus in rats

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