1. Faculty of Psychology and Neuroscience
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Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG: Evidence for an interaction between acetylcholine and serotonin?
Laura G.J.M. BorghansA, A. BloklandA, A. SambethA
A Department of Neuropsychology and Psychopharmacology, Maastricht University, The Netherlands
Background
Although most research has investigated the role of acetylcholine in Alzheimer’s Disease (AD), cognitive impairments in AD may not be limited to impaired cholinergic functioning. AD is associated with a decrease in different neurotransmitters, including serotonin and noradrenaline. Moreover, these neurotransmitters have also been found to play a role in cognitive functions. To study the interaction between neurotransmitters such as acetylcholine and serotonin, pharmacological models can be applied.
Traditionally the nonselective cholinergic antagonist scopolamine has been used as a pharmacological model to mimic episodic memory impairments as seen in dementia1. Since biperiden is more selective it may therefore have less peripheral side effects. For biperiden similar memory impairing effects have been found in humans2.
It has been established that acute tryptophan depletion (ATD) impairs episodic memory functioning in patients as well as in healthy subjects3.
Objective
To further examine the effects of the M1 antagonist biperiden, acute tryptophan depletion (ATD) and the interaction between both on a Verbal Learning Task in combination with electroencephalography.
Objective
To further examine the effects of the M1 antagonist biperiden, ATD and the interaction between both on a verbal learning task (VLT) in combination with electroencephalography (EEG).
Methods
The study was conducted according a double-blind, placebo controlled, 4-way crossover design. Seventeen participants received biperiden (2.0mg), ATD (SolugelP), a combination of both or a placebo in counterbalanced order with a wash out of at least 7 days.
A VLT was performed while recording EEG. The task consisted of an immediate and delayed recall as well as a recognition part.
ATD TRP+ or TRP-
Biperiden
2.0 or 0 mg
VLT encoding & immediate recall
3 trials
VLT delayed recall
& recognition
Time
Grand average across participants of the ERP’s elicited by the treatments at the Cz electrode during the encoding phase previous to the immediate recall.
Number of words recalled during each immediate recall trial (A); The total number of words recalled during the three immediate recall trials (B); The number of words recalled during the delayed recall.
Results
Biperiden significantly decreased the scores for the delayed recall but not for the immediate recall.
ATD resulted in lower scores for the immediate recall as well as for the delayed recall.
The combination of biperiden and ATD did not impair the memory performance more than for each treatment alone  no interactions between biperiden and ATD were found.
Analysis of the EEG data revealed significant interactions between biperiden and ATD for the amplitude of the P3b, N400 and P600 components for the acquisition phase of the VLT.
Conclusion
This study does not support the notion that the serotonergic and cholinergic systems interact in processes related to learning and memory on the behavioral level.
On the electrophysiological level there are indications that a possible interaction exists.
The current findings are not in line with animal studies that show clear interactions between acetylcholine and serotonin.
References
Ebert U, Kirch W (1998) Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest 28:
Sambeth A, Riedel WJ, Klinkenberg I, Kahkonen S, Blokland A (2015) Biperiden selectively induces memory impairment in healthy volunteers: no interaction with citalopram. Psychopharmacology (Berl) 232:
Mendelsohn D, Riedel WJ, Sambeth A (2009) Effects of acute tryptophan depletion on memory, attention and executive functions: a systematic review. Neurosci Biobehav Rev 33:
Correspondence to: Laura Borghans
Dept of Neuropsychology & Psychopharmacology T
Maastricht University, P.O. Box MD Maastricht, The Netherlands