Age-related emotionality is associated with cortical δ-opioid receptor dysfunction-dependent astrogliosis

Multiple changes occur in the aging brain, leading to age-related emotional disorders. A growing body of recent evidence suggests that the cortical δ-opioid receptor system plays a critical role in anxiety- and depressive-like behaviors in the rodent. In this study, we show that aging mice promoted anxiety-like behaviors as characterized by both the light–dark and elevated plus-maze tests, and they exhibit an increase in astrocytes in the cingulate cortex due to the dysfunction of cortical δ-opioid receptor systems. As well as aging mice, mice with a dysfunction of the δ-opioid receptor system induced by chronic treatment with the selective δ-opioid receptor antagonist naltrindole, revealed astrogliosis in the cingulate cortex, which was associated with anxiety. We also found that the microinjection of cultured astrocytes into the cingulate cortex of young mice enhanced the expression of anxiety-like behavior. Our results indicate that the aging process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical δ-opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety during normal aging.