Differential Effects of Scopolamine and Lorazepam on Working Memory Maintenance versus Manipulation Processes

By Mintzer, Miriam Z.; Griffiths, Roland R. | Cognitive, Affective and Behavioral Neuroscience, June 2007 | Go to article overview

Differential Effects of Scopolamine and Lorazepam on Working Memory Maintenance versus Manipulation Processes


Mintzer, Miriam Z., Griffiths, Roland R., Cognitive, Affective and Behavioral Neuroscience


Between-study comparisons of benzodiazepine and anticholinergic drugs on working memory suggest that anticholinergics may produce greater impairment in maintenance processes, whereas benzodiazepines may produce greater impairment in manipulation processes. This study directly compared acute effects of the benzodiazepine lorazepam (1.0 and 2.0 mg/70 kg, orally administered) and the anticholinergic scopolamine (0.25 and 0.50 mg/ 70 kg, subcutaneously administered) on working memory maintenance (storage and rehearsal) and manipulation processes in a placebo-controlled, double-dummy, double-blind, crossover design in 20 healthy volunteers. Using a modified Sternberg paradigm, storage, rehearsal, and manipulation processes were parametrically manipulated by varying memory load, delay between stimulus presentation and test, and number of operations performed on the letter strings, respectively, while controlling for drug effects on nonmemory processes. As predicted, the results suggested greater impairment in maintenance processes (rehearsal) with scopolamine than with lorazepam and greater impairment in manipulation processes with lorazepam than with scopolamine. In addition, the results suggested greater overall slowing of working memory processes with lorazepam.

It is well established that benzodiazepine (e.g., diazepam, or Valium; lorazepam, or Ativan) and anticholinergic (e.g., scopolamine) drugs induce temporary amnesia when administered acutely to healthy volunteers (for reviews, see Curran, 1991, 2000; Kopelman, 1986; Polster, 1993). Several researchers (Duka, Curran, Rusted, & Weingartner, 1996; Hirshman, Passannante, & Arndt, 2001; Mintzer & Griffiths, 2001b; Polster, 1993; Reder et al., 2006) have argued that, like neuropsychological studies of brain-damaged patients, which have played a critical role in advancing the understanding of normal and abnormal memory mechanisms, investigation of drug-induced amnesia can also be a powerful tool for elucidating memory mechanisms. In fact, investigation of drug-induced amnesia has several distinct advantages over traditional studies of amnesic patients. Most importantly, unlike the memory deficits found in amnesic patients, effects of drugs on memory processes are reversible and can be empirically manipulated in controlled laboratory experiments with large numbers of healthy volunteers. Furthermore, the quantitative dosing properties of drugs can be exploited to produce a graded amnesic effect in a dose-effect design. Findings of selective effects of drugs on particular aspects of memory performance but not others, or of dissociations between drugs, can provide converging evidence with data from nonpharmacological studies for the dissociability of specific processes or subcomponents (see Hirshman, Fisher, Henthorn, Arndt, & Passannante, 2002; Hirshman et al., 2001; Mintzer, 2003; Mintzer & Griffiths, 2001b). In addition, comparison of memory-impairing drugs with distinct neurochemical or pharmacological mechanisms of action can elucidate the brain mechanisms underlying specific cognitive processes.

The present experiment was designed to compare the acute effects of the benzodiazepine lorazepam and the anticholinergic scopolamine on working memory processes. Benzodiazepines facilitate the action of gammaaminobutyric acid (GABA) by acting as agonists at specific sites on the GABA^sub A^ receptor complex (Mohler & Okada, 1977; Squires & Braestrup, 1977), whereas scopolamine inhibits the action of acetylcholine by acting as an antagonist at muscarinic cholinergic receptors (Ketchum, Sidell, Crowell, Aghajanian, & Haines, 1973). Working memory refers to the temporary maintenance and online manipulation of a limited amount of information in the service of current behavioral goals (Baddeley, 1986, 1992; for recent reviews, see D'Esposito, 2001; Smith & Jonides, 1998). The concept of working memory was originally introduced by Baddeley (1986) and replaced earlier conceptualizations of a unitary, passive, short-term storage system (Atkinson & Shifrrin, 1968). …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

Differential Effects of Scopolamine and Lorazepam on Working Memory Maintenance versus Manipulation Processes
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen
Items saved from this article
  • Highlights & Notes
  • Citations
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Search by... Author
    Show... All Results Primary Sources Peer-reviewed

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.