title: Biperiden selectively induces memory impairment in healthy volunteers: no interaction with citalopram.
abstract: BACKGROUND
  Traditionally, the non-selective muscarinic antagonist scopolamine has been used to induce episodic memory impairments as found in Alzheimer's disease (AD). However, it also impairs attention and induces drowsiness. Muscarinic antagonists more selective for the M1 receptor might, therefore, be preferred.
  
  
  OBJECTIVE
  We examined the effects of the M1 antagonist biperiden on cognitive functions in order to test the specificity of this drug on memory performance. Additionally, we assessed whether the selective serotonin re-uptake inhibitor citalopram can reverse a possible biperiden-induced impairment.
  
  
  METHODS
  The study was conducted according to a double-blind, placebo-controlled, four-way cross-over design. Sixteen volunteers received biperiden (2 mg), citalopram (20 mg), a combination of the two, or a placebo in counterbalanced order with a washout of at least 4 days. Cognitive tests (verbal memory, continuous recognition memory, spatial memory, choice reaction) were performed 4 and 1 h after treatment with citalopram and biperiden, respectively.
  
  
  RESULTS
  Biperiden impaired memory performance in the verbal learning task, the continuous recognition memory test, and the spatial memory task. Effects on attention and side effects, as measured using the choice reaction time test and questionnaires respectively, could be neglected. Citalopram did not affect any of the memory or attention measures taken. Most importantly, citalopram was also unable to reverse the biperiden-induced memory impairments.
  
  
  CONCLUSIONS
  Our results, thus, show that the M1 antagonist biperiden may serve as a translational model to induce episodic memory deficits as seen in AD. However, the interactive influence of acetylcholine and serotonin on memory could not be confirmed.
authors.affiliation: Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, The Netherlands, anke.sambeth@maastrichtuniversity.nl.
authors.forename: Anke
authors.initials: A
authors.lastname: Sambeth
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Riedel
authors.forename: Inge
authors.initials: I
authors.lastname: Klinkenberg
authors.forename: Seppo
authors.initials: S
authors.lastname: Kähkönen
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000139:chemically induced / Q000523:psychology; D001288:Attention / Q000187:drug effects; D001712:Biperiden / Q000633:toxicity*; D015283:Citalopram / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000175:diagnosis; D011939:Mental Recall / Q000187:drug effects; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D015283:Citalopram; D001712:Biperiden