Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs

Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2′-chloroet...

Full description

Bibliographic Details
Main Authors: Berger, Joel I., Coomber, Ben, Hill, Samantha, Alexander, Stephen, Owen, William, Palmer, Alan R., Wallace, Mark N.
Format: Article
Published: Elsevier 2017
Subjects:
Online Access:https://eprints.nottingham.ac.uk/47930/
_version_ 1848797652315013120
author Berger, Joel I.
Coomber, Ben
Hill, Samantha
Alexander, Stephen
Owen, William
Palmer, Alan R.
Wallace, Mark N.
author_facet Berger, Joel I.
Coomber, Ben
Hill, Samantha
Alexander, Stephen
Owen, William
Palmer, Alan R.
Wallace, Mark N.
author_sort Berger, Joel I.
building Nottingham Research Data Repository
collection Online Access
description Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2′-chloroethylamide (ACEA), a highly-selective CB1 agonist, could attenuate a variety of auditory effects caused by prior administration of salicylate, and potentially treat tinnitus. We recorded cortical resting-state activity, auditory-evoked cortical activity and auditory brainstem responses (ABRs), from chronically-implanted awake guinea pigs, before and after salicylate + ACEA. Salicylate-induced reductions in click-evoked ABR amplitudes were smaller in the presence of ACEA, suggesting that the ototoxic effects of salicylate were less severe. ACEA also abolished salicylate-induced changes in cortical alpha band (6-10 Hz) oscillatory activity. However, salicylate-induced increases in cortical evoked activity (suggestive of the presence of hyperacusis) were still present with salicylate + ACEA. ACEA administered alone did not induce significant changes in either ABR amplitudes or oscillatory activity, but did increase cortical evoked potentials. Furthermore, in two separate groups of non-implanted animals, we found no evidence that ACEA could reverse behavioural identification of salicylate- or noise-induced tinnitus. Together, these data suggest that while ACEA may be potentially otoprotective, selective CB1 agonists are not effective in diminishing the presence of tinnitus or hyperacusis.
first_indexed 2025-11-14T20:07:17Z
format Article
id nottingham-47930
institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T20:07:17Z
publishDate 2017
publisher Elsevier
recordtype eprints
repository_type Digital Repository
spelling nottingham-479302020-05-04T19:14:30Z https://eprints.nottingham.ac.uk/47930/ Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs Berger, Joel I. Coomber, Ben Hill, Samantha Alexander, Stephen Owen, William Palmer, Alan R. Wallace, Mark N. Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2′-chloroethylamide (ACEA), a highly-selective CB1 agonist, could attenuate a variety of auditory effects caused by prior administration of salicylate, and potentially treat tinnitus. We recorded cortical resting-state activity, auditory-evoked cortical activity and auditory brainstem responses (ABRs), from chronically-implanted awake guinea pigs, before and after salicylate + ACEA. Salicylate-induced reductions in click-evoked ABR amplitudes were smaller in the presence of ACEA, suggesting that the ototoxic effects of salicylate were less severe. ACEA also abolished salicylate-induced changes in cortical alpha band (6-10 Hz) oscillatory activity. However, salicylate-induced increases in cortical evoked activity (suggestive of the presence of hyperacusis) were still present with salicylate + ACEA. ACEA administered alone did not induce significant changes in either ABR amplitudes or oscillatory activity, but did increase cortical evoked potentials. Furthermore, in two separate groups of non-implanted animals, we found no evidence that ACEA could reverse behavioural identification of salicylate- or noise-induced tinnitus. Together, these data suggest that while ACEA may be potentially otoprotective, selective CB1 agonists are not effective in diminishing the presence of tinnitus or hyperacusis. Elsevier 2017-10-31 Article PeerReviewed Berger, Joel I., Coomber, Ben, Hill, Samantha, Alexander, Stephen, Owen, William, Palmer, Alan R. and Wallace, Mark N. (2017) Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs. Hearing Research . ISSN 1878-5891 Tinnitus; cannabinoids; chronic recording; auditory cortex; treatment; salicylate http://www.sciencedirect.com/science/article/pii/S0378595517303593 doi:10.1016/j.heares.2017.10.012 doi:10.1016/j.heares.2017.10.012
spellingShingle Tinnitus; cannabinoids; chronic recording; auditory cortex; treatment; salicylate
Berger, Joel I.
Coomber, Ben
Hill, Samantha
Alexander, Stephen
Owen, William
Palmer, Alan R.
Wallace, Mark N.
Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
title Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
title_full Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
title_fullStr Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
title_full_unstemmed Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
title_short Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
title_sort effects of the cannabinoid cb1 agonist acea on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs
topic Tinnitus; cannabinoids; chronic recording; auditory cortex; treatment; salicylate
url https://eprints.nottingham.ac.uk/47930/
https://eprints.nottingham.ac.uk/47930/
https://eprints.nottingham.ac.uk/47930/