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Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test.

Arya Rahbarnia, Zhaoxia Li, Paul J Fletcher

Psychopharmacology October 19, 2023 DOI: 10.1007/s00213-023-06474-9 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Mice
Interventions Psilocybin TCB-2 M100907
Dose 0.3, 1, and 3 mg/kg for psilocybin and TCB-2; 0.1, 0.3, and 1 mg/kg for M100907
Topics Psilocybin Serotonin
Keywords 5-ht2a Continuous performance test Locomotion M100907 Tcb-2 Psychedelics hallucinogens Entheogens Serotonergic compounds Attention cognition Focus Vigilance Behavioral pharmacology psychopharmacology Visual attention
Citations 9
Key findings Psilocybin, TCB-2, and M100907 impaired performance on the rodent continuous performance task, but these effects may be partly due to drug-induced locomotor changes, providing little support for psilocybin altering visual attention or 5-HT2A receptor modulation of attention.

Abstract

Neuropsychiatric disorders such as depression are characterized in part by attention deficits. Attention is modulated by the serotonin (5-HT) neurotransmitter system. The 5-HT2A agonist and hallucinogen psilocybin (PSI) is a promising treatment for disorders characterized by attention changes. However, few studies have investigated PSI's direct effect on attention. Using the rodent continuous performance task (CPT), we assessed PSI's effect on attention. We also evaluated the impact of 5-HT2A receptor agonist TCB-2 and antagonist M100907 for comparative purposes. In the CPT, mice learned to distinguish visual targets from non-targets for milkshake reward. Performance was then tested following injections of PSI (0.3, 1, and 3 mg/kg), TCB-2 (0.3, 1, and 3 mg/kg), or M100907 (0.1, 0.3, and 1 mg/kg). Subsequently, drug effects were then evaluated using a more difficult CPT with variable stimulus durations. Mice were then tested on the CPT following repeated PSI injections. Drug effects on locomotor activity were also measured. In the CPT, all three drugs reduced hit and false alarm rate and induced conservative responding. PSI also reduced target discrimination. These effects were seen primarily at doses that also significantly reduced locomotor activity. No drug effects were seen on the more difficult CPT or following repeated PSI injections. Psilocybin, TCB-2, and M100907 impaired performance of the CPT. However, this may be in part due to drug-induced locomotor changes. The results provide little support for the idea that psilocybin alters visual attention, or that 5-HT2A receptors modulate this process.

Comparable studies

Other preclinical and animal studies on serotonin, most cited first.

Study Year Design Participants
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice 2021 Observational cohort
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models 2023 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study

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Psilocybin Serotonin Depression