The processing of novel stimuli is known to take place in the hippocampus and frontal cortex, and is influenced by the cholinergic system. This ability is crucial to help detect changes in the environment and adapt behaviour accordingly. Previous research has shown that acetylcholine (ACh) can interact with serotonin (5-HT) at the hippocampal level, which may have consequences for cognitive functioning. However, little is known about the exact nature of this ACh and 5-HT interaction as well their possible interactive effects on novelty processing. We investigated the interactive role of ACh and 5-HT in novelty processing in healthy young participants. Levels of these neurotransmitters were manipulated with the muscarinic M1 antagonist biperiden, and with acute tryptophan depletion (ATD). Participants received either placebo, biperiden, ATD, or a combination of both in a double-blind cross-over design. Auditory event-related potentials (ERPs) were recorded while a novelty oddball task was presented. Our results showed that biperiden affected ERP components considered to reflect attentional mechanisms; it increased the P50 amplitude and decreased that of the P200. Furthermore, a decrease of N100 amplitude by ATD was reversed by biperiden. The treatments did not affect the mismatch negativity (MMN) component, which is elicited when a deviant stimulus is presented in a sequence of repetitive stimuli. Importantly, biperiden decreased the amplitude of the ERP component related to novelty processing (P3a). The current study's results did not reveal an interactive effect of ACh and 5-HT on novelty processing. However, the data do suggest that ACh is involved in novelty processing and that it influences basic stimulus processing, without affecting sound-discrimination accuracy.
Keywords: Acetylcholine; Acute tryptophan depletion; Biperiden; Novelty oddball; P3a; Serotonin.
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