TY - JOUR
T1 - Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress
T2 - Potential relevance of limbic GAD
AU - Ortiz, J. Bryce
AU - Taylor, Sara B.
AU - Hoffman, Ann N.
AU - Campbell, Alyssa N.
AU - Lucas, Louis R.
AU - Conrad, Cheryl
N1 - Funding Information:
The authors gratefully acknowledge the contributions of Danya P. Anouti, Amanda Krigbaum, Agnieszka Mika, and Jeffery J. Hanna for their assistance with the study. This work was funded in part by Arizona State University's College of Liberal Arts and Sciences (Conrad), Loyola University Research Support (Lucas), the National Institutes of Health Initiative to Maximize Student Development program ( R25GM099650 to Stuart Newfeld for funding Ortiz), and the National Science Foundation Graduate Research Fellowship Program ( DGE-1311230 , Ortiz).
Publisher Copyright:
© 2014 Elsevier B.V..
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.
AB - Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.
KW - Amygdala
KW - Chronic stress
KW - GABA
KW - Hippocampus
KW - Recovery
KW - Sex differences
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U2 - 10.1016/j.bbr.2014.12.051
DO - 10.1016/j.bbr.2014.12.051
M3 - Article
C2 - 25591480
AN - SCOPUS:84936972661
SN - 0166-4328
VL - 282
SP - 176
EP - 184
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -