Effects of Acute Lorazepam Administration on Aminergic Activity in Normal Elderly Subjects: Relationship to Performance Effects and Apolipoprotein Genotype

Author： Pomara Nunzio Willoughby Lisa M. Hashim Audrey Sershen Henry Sidtis John J. Wesnes Keith Greenblatt David J. Lajtha Abel

Publisher： Springer Publishing Company

ISSN： 0364-3190

Source： Neurochemical Research, Vol.29, Iss.7, 2004-07, pp. : 1391-1398

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Abstract

The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-ε4 allele were examined. Eighteen healthy elderly (8 ε4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of ε4 status. However, the 1.0 mg dose increased p5-HIAA in ε4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The ε4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.