Acetaminophen affects the duration but not the occurrence of BOLD signal decline in the dorsal hippocampus after induction of neuronal afterdischarges.

Combined in vivo electrophysiological and functional magnetic resonance imaging (fMRI) measurements were used to monitor neuronal and hemodynamic responses in the right dorsal hippocampus during and after electrical stimulation of the right perforant pathway with a short period of 20 Hz pulses. These measurements were performed under two conditions: 1.5% isoflurane (which has a long-term vasodilator effect) or 100 µg/kg medetomidine (which has a long-term vasoconstrictor effect). The stimulation elicited a short period of neuronal afterdischarges (nAD) followed by a sustained decline in fMRI BOLD signals, as previously described (Arboit et al., 2024). While the duration of nAD was similar in presence of isoflurane and medetomidine, the subsequent decline of BOLD signal was significantly longer with isoflurane than with medetomidine. However, when the same experiments were performed in the presence of acetaminophen, the duration of the sustained decline of BOLD signals became similar: acetaminophen significantly prolonged the decline in the presence of medetomidine, whereas it only slightly shortened it in the presence of isoflurane. As acetaminophen did not affect the generation and intensity of nAD, the results indicate that nAD activates at least two different neurovascular coupling (NVC) mechanisms that mediate the sustained BOLD signal decline, of which acetaminophen affects the maintenance.