TY - JOUR
T1 - Glucocorticoid-induced impairment in declarative memory performance in adult humans
AU - Newcomer, J. W.
AU - Craft, S.
AU - Hershey, T.
AU - Askins, K.
AU - Bardgett, M. E.
PY - 1994/4
Y1 - 1994/4
N2 - Glucocorticoids (GCs) have a variety of effects on the brain including site-preferential, inhibitory effects on hippocampal neurons. In the case of dexamethasone (DEX), extended rather than single-dose treatment in vivo may be required for binding to brain rather than peripheral (e.g., pituitary) GC receptors and for maximizing other biologic effects in hippocampus (e.g., GC receptor downregulation, inhibition of glucose transport). Based on the contributory role of hippocampal neurons in declarative memory performance, we investigated the cognitive consequences of DEX treatment in normal adult human subjects, hypothesizing a decrease in declarative memory performance after extended but not overnight treatment. Double-blind, placebo-controlled treatment with DEX was given at 2300 hr for four consecutive days (0.5, 1, 1, 1 mg, respectively). Plasma sampling (0800 and 1600 hr) and cognitive testing (1600 hr) were performed on study days 0 (baseline), 1, and 4, and 7 d posttreatment. Repeated-measures ANOVA found a significant interaction between study day and treatment condition for correct recall during a paragraph recall task [F(3,51) = 3.52, p = 0.02]. DEX (n = 10) in comparison to placebo (n = 9) treatment decreased correct paragraph recall on study day 4 [F(1,17) = 5.01, p = 0.04] and study day 11 [F(1,17) = 5.82, p = 0.03], with the lowest level of performance occurring on day 4 followed by a return toward baseline performance level by day 11. In the placebo-treated subjects, correct paragraph recall improved over the course of treatment, consistent with practice. No other cognitive measure was affected by DEX treatment, arguing against a nonspecific DEX effect on arousal or attention. Plasma cortisol concentrations were maximally suppressed at study day 4, consistent with GC receptor binding by DEX.
AB - Glucocorticoids (GCs) have a variety of effects on the brain including site-preferential, inhibitory effects on hippocampal neurons. In the case of dexamethasone (DEX), extended rather than single-dose treatment in vivo may be required for binding to brain rather than peripheral (e.g., pituitary) GC receptors and for maximizing other biologic effects in hippocampus (e.g., GC receptor downregulation, inhibition of glucose transport). Based on the contributory role of hippocampal neurons in declarative memory performance, we investigated the cognitive consequences of DEX treatment in normal adult human subjects, hypothesizing a decrease in declarative memory performance after extended but not overnight treatment. Double-blind, placebo-controlled treatment with DEX was given at 2300 hr for four consecutive days (0.5, 1, 1, 1 mg, respectively). Plasma sampling (0800 and 1600 hr) and cognitive testing (1600 hr) were performed on study days 0 (baseline), 1, and 4, and 7 d posttreatment. Repeated-measures ANOVA found a significant interaction between study day and treatment condition for correct recall during a paragraph recall task [F(3,51) = 3.52, p = 0.02]. DEX (n = 10) in comparison to placebo (n = 9) treatment decreased correct paragraph recall on study day 4 [F(1,17) = 5.01, p = 0.04] and study day 11 [F(1,17) = 5.82, p = 0.03], with the lowest level of performance occurring on day 4 followed by a return toward baseline performance level by day 11. In the placebo-treated subjects, correct paragraph recall improved over the course of treatment, consistent with practice. No other cognitive measure was affected by DEX treatment, arguing against a nonspecific DEX effect on arousal or attention. Plasma cortisol concentrations were maximally suppressed at study day 4, consistent with GC receptor binding by DEX.
KW - cognitive
KW - cortisol
KW - declarative memory
KW - dexamethasone
KW - glucocorticoid
KW - hippocampus
KW - memory
UR - http://www.scopus.com/inward/record.url?scp=0028348227&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.14-04-02047.1994
DO - 10.1523/jneurosci.14-04-02047.1994
M3 - Article
C2 - 8198631
AN - SCOPUS:0028348227
SN - 0270-6474
VL - 14
SP - 2047
EP - 2053
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 4
ER -