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The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats

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Abstract

Rationale

The hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is structurally similar to other indoleamine hallucinogens such as LSD. The present study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (PPI) paradigm.

Objectives

A series of interaction studies using the serotonin (5-HT)1A antagonist WAY-100635 (1.0 mg/kg), the 5-HT2A antagonist M100907 (1.0 mg/kg), and the 5-HT2C antagonist SER-082 (0.5 mg/kg) were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) in the BPM and PPI paradigms.

Results

5-MeO-DMT decreased locomotor activity, investigatory behavior, the time spent in the center of the BPM chamber, and disrupted PPI. All of these effects were antagonized by WAY-100635 pretreatment. M100907 pretreatment failed to attenuate any of these effects, while SER-082 pretreatment only antagonized the PPI disruption produced by 5-MeO-DMT.

Conclusions

While the prevailing view was that the activation of 5-HT2 receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-HT1A receptors in the effects of the indoleamine hallucinogen 5-MeO-DMT on locomotor activity and PPI in rats.

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Acknowledgements

This work was supported by National Institute on Drug Abuse Award R02 DA02925 and the Veterans Affairs VISN 22 Mental Illness Research, Education, and Clinical Center. M. A. Geyer holds an equity position in San Diego Instruments. These studies were conducted while E. M. Ruiz was conducting an externship from the School of Pharmacy, University of Utrecht, The Netherlands. These experiments comply with the current laws of the United States.

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  1. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA

    Kirsten Krebs-Thomson, Erbert M. Ruiz, Virginia Masten, Mahalah Buell & Mark A. Geyer

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  1. Kirsten Krebs-Thomson
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  2. Erbert M. Ruiz
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  3. Virginia Masten
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  5. Mark A. Geyer
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Correspondence to Mark A. Geyer.

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Krebs-Thomson, K., Ruiz, E.M., Masten, V. et al. The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats. Psychopharmacology 189, 319–329 (2006). https://doi.org/10.1007/s00213-006-0566-1

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