RT Journal Article
SR Electronic
T1 Pairing with Enriched Sound Exposure Restores Auditory Processing Degraded by an Antidepressant
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2850
OP 2859
DO 10.1523/JNEUROSCI.2027-22.2023
VO 43
IS 16
A1 Cheng, Yuan
A1 Chen, Ruru
A1 Su, Bowen
A1 Zhang, Guimin
A1 Sun, Yutian
A1 An, Pengying
A1 Fang, Yue
A1 Zhang, Yifan
A1 Shan, Ye
A1 de Villers-Sidani, Étienne
A1 Wang, Yunfeng
A1 Zhou, Xiaoming
YR 2023
UL http://www.jneurosci.org/content/43/16/2850.abstract
AB Antidepressants, while effective in treating depression and anxiety disorders, also induce deficits in sensory (particularly auditory) processing, which in turn may exacerbate psychiatric symptoms. How antidepressants cause auditory signature deficits remains largely unknown. Here, we found that fluoxetine-treated adult female rats were significantly less accurate when performing a tone-frequency discrimination task compared with age-matched control rats. Their cortical neurons also responded less selectively to sound frequencies. The degraded behavioral and cortical processing was accompanied by decreased cortical perineuronal nets, particularly those wrapped around parvalbumin-expressing inhibitory interneurons. Furthermore, fluoxetine induced critical period-like plasticity in their already mature auditory cortices; therefore, a brief rearing of these drug-treated rats under an enriched acoustic environment renormalized auditory processing degraded by fluoxetine. The altered cortical expression of perineuronal nets was also reversed as a result of enriched sound exposure. These findings suggest that the adverse effects of antidepressants on auditory processing, possibly because of a reduction in intracortical inhibition, can be substantially alleviated by simply pairing drug treatment with passive, enriched sound exposure. They have important implications for understanding the neurobiological basis of antidepressant effects on hearing and for designing novel pharmacological treatment strategies for psychiatric disorders.SIGNIFICANCE STATEMENT Clinical experience suggests that antidepressants adversely affect sensory (particularly auditory) processing, which can exacerbate patients' psychiatric symptoms. Here, we show that the antidepressant fluoxetine reduces cortical inhibition in adult rats, leading to degraded behavioral and cortical spectral processing of sound. Importantly, fluoxetine induces a critical period-like state of plasticity in the mature cortex; therefore, a brief rearing under an enriched acoustic environment is sufficient to reverse the changes in auditory processing caused by the administration of fluoxetine. These results provide a putative neurobiological basis for the effects of antidepressants on hearing and indicate that antidepressant treatment combined with enriched sensory experiences could optimize clinical outcomes.