Aging affects isoproterenol-induced water drinking, astrocyte density, and central neuronal activation in female Brown Norway rats

Rachel N. Hardy, Zinar D. Simsek, Brandon Curry, Sheri L. Core, Terry Beltz, Baojian Xue, Alan K. Johnson, Robert L. Thunhorst, Kathleen Curtis

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Age-dependent impairments in the central control of compensatory responses to body fluid challenges have received scant experimental attention, especially in females. In the present study, we found that water drinking in response to β-adrenergic activation with isoproterenol (30 μg/kg, s.c.) was reduced by more than half in aged (25 mo) vs. young (5 mo) ovariectomized female Brown Norway rats. To determine whether this age-related decrease in water intake was accompanied by changes in central nervous system areas associated with fluid balance, we assessed astrocyte density and neuronal activation in the SFO, OVLT, SON, AP and NTS of these rats using immunohistochemical labeling for GFAP and c-fos, respectively. GFAP labeling intensity was increased in the SFO, AP, and NTS of aged females independent of treatment, and was increased in the OVLT of isoproterenol-treated rats independent of age. Fos immunolabeling in response to isoproterenol was reduced in both the SFO and the OVLT of aged females compared to young females, but was increased in the SON of female rats of both ages. Finally, fos labeling in the AP and caudal NTS of aged rats was elevated after vehicle control treatment and did not increase in response to isoproterenol as it did in young females. Thus, age-related declines in water drinking are accompanied by site-specific, age-related changes in astrocyte density and neuronal activation. We suggest that astrocyte density may alter the detection and/or processing of signals related to isoproterenol treatment, and thereby alter neuronal activation in areas associated with fluid balance.

Original languageEnglish
Pages (from-to)90-97
Number of pages8
JournalPhysiology and Behavior
Publication statusPublished - 1 Aug 2018



  • Area postrema
  • Nucleus of the solitary tract
  • Organum vasculosum of the lamina terminalis
  • Subfornical organ
  • Supraoptic nucleus

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