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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

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Abstract

Rationale

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.

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

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Data availability

Data are available upon request.

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Authors and Affiliations

  1. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Arya Rahbarnia, Zhaoxia Li & Paul J. Fletcher

  2. Department of Psychology, University of Toronto, Toronto, ON, Canada

    Arya Rahbarnia & Paul J. Fletcher

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Paul J. Fletcher

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  1. Arya Rahbarnia
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  2. Zhaoxia Li
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Correspondence to Arya Rahbarnia.

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Rahbarnia, A., Li, Z. & Fletcher, P.J. 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. Psychopharmacology (2023). https://doi.org/10.1007/s00213-023-06474-9

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