Rationale: 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.
Objectives: 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.