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Abstract:
Goal: Working memory processes are mediated by the prefrontal
cortex (D'Esposito et al. 2000) and modulated by monoamine
neurotransmitters (Arnsten 1999). To further investigate the
effects of noradrenergic stimulation and blockade two
pharmacological studies were performed. Methods: A total of 40
healthy students were investigated. The first study compared two
beta-blockers with different liposolubility (50 mg of atenolol vs.
25 mg of propranolol) and placebo. In the second study a
noradrenergic psychostimulant drug (200 mg of modafinil) was
administered, again in a balanced double-blind placebo-controlled
design. Drug effects were confirmed by cardiocirculatory monitoring
or plasma concentrations. Manipulation processes were investigated
with a verbal working memory paradigm that requires short-term
storage and cued manipulations of four-digit-sequences (Bublak et
al. 2000). Results: There were higher (p<0.05) manipulation
costs after propranolol as compared to atenolol or placebo. The
effect was only observed in low anxiety subjects. In study two
there was a reduction of errors in the manipulation conditions but
not in the no-manipulation condition after modafinil (p<0.01).
Attentional control tasks (letter cancellation, trail-making) were
not affected by any of the drugs. Conclusion: Noradrenergic
blockade and stimulation affect manipulation processes in working
memory bidirectionally. Our data indicate central effects that
depend on endogenous activity of the noradrenergic system as well
as complex interactions between arousal and working memory
processes.
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