No interaction between rivastigmine and citalopram on memory and novelty processing in healthy human volunteers

BACKGROUND: Animal literature suggests an interaction between acetylcholine and serotonin on cognitive functions. AIMS: The aim of the current study was to assess whether both neurotransmitters interact during memory and novelty processing in humans. METHODS: We tested the interaction between acetylcholine and serotonin on cognitive functions in healthy volunteers by means of treatment with rivastigmine and citalopram, respectively. RESULTS: The main result of the study showed that during the verbal learning task participants significantly recalled fewer words after citalopram treatment than after rivastigmine or placebo during both the immediate and delayed recall tasks. Rivastigmine was not able to reverse the impairing effect of citalopram. CONCLUSIONS: This finding is in line with previous studies in which we manipulated acetylcholine and serotonin in different manners. Taken together, these studies in humans do not support the notion from animal studies that these two neurotransmitters interact on cognitive functions

Phosphodiesterase 4 inhibition affects both the direct and indirect pathway:an electrophysiological study examining the tri-phasic response in the substantia nigra pars reticulata

Fronto-striatal circuits constitute the neurobiological basis of many neuropsychiatric disorders. Part of the intracellular signaling within these circuits, including its dopaminergic modulation, is regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling cascade. Based on the overall expression in human fronto-striatal circuitry, we tested the effects of a cAMP selective phosphodiesterase 4 (PDE4) inhibitor on the tri-phasic response in the dorsomedial substantia nigra pars reticulata (SNr) upon stimulation of the infralimbic cortex in rats. Our results show for the first time that stimulation of the cognitive infralimbic cortex leads to a tri-phasic response in SNr neurons. In addition and in line with previous biochemical and behavioral studies, PDE4 inhibition by roflumilast affects the direct pathway as well as the indirect pathway of which the latter appears more sensitive than the former