Abstract
AbstractPsychedelics are attractive potential therapeutic agents for treatment resistant depression due to their rapid and sustained effects. These effects have been largely attributed to serotonin (5-hydroxytryptamine) receptor agonism, especially at the 5-HT2Areceptor (5-HT2AR). Recent human functional neuroimaging studies report dramatic 5-HT2AR-dependent changes in behavior and functional network organization that presumably reflect neuromodulatory effects. However, serotonin also has potent vasoactive effects that have not been assessed in prior imaging studies of classic (i.e., 5-HT2AR agonists) psychedelics. We assessed the neural, hemodynamic, and neurovascular coupling (NVC) effects of the hallucinogenic 5-HT2Areceptor agonist, 2,5-Dimethoxy-4-iodoamphetamine (DOI), using wide-field optical imaging (WFOI) in mice during both awake, whisker stimulation and under awake, resting-state conditions. Under both task and resting-state conditions, DOI narrowed hemodynamic response functions and enhanced transduction of neuronal activity in the delta band. These effects were regionally specific and strongest in association regions. Co-administration of DOI and 5-HT2aR antagonist, MDL100907, reversed the effects of DOI on NVC. These DOI-induced NVC alterations imply a dissociation between neuronal versus hemodynamic signals and emphasize the need to consider the neurovascular effects of psychedelics when interpreting hemodynamic measures of neuronal activity.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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