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Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors

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Abstract

Rationale

The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity.

Objective

The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the behavioral pattern monitor, which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)1A antagonist WAY-100635 (1.0 mg/kg) and the 5-HT2A antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals.

Results

5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAOA inhibitor clorgyline, whereas the selective MAOB inhibitor (−)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity.

Conclusions

The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by the inhibition of MAOA. Furthermore, 5-HT2A receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAOA inhibitors.

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Acknowledgements

This work was supported by National Institute on Drug Abuse Award 5R01 DA02925 and the Veterans Affairs VISN 22 Mental Illness Research, Education, and Clinical Center. The authors wish to thank Erbert M. Ruiz and Dr. Kirsten Krebs-Thomson for their assistance with this project. These experiments comply with the current laws of the United States.

Disclosure/conflict of interest

The authors have no conflict of interest, financial or otherwise, to declare.

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Authors and Affiliations

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

    Adam L. Halberstadt, Mahalah R. Buell, Virginia L. Masten, Victoria B. Risbrough & Mark A. Geyer

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  1. Adam L. Halberstadt
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  2. Mahalah R. Buell
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  3. Virginia L. Masten
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Correspondence to Mark A. Geyer.

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Halberstadt, A.L., Buell, M.R., Masten, V.L. et al. Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors. Psychopharmacology 201, 55–66 (2008). https://doi.org/10.1007/s00213-008-1247-z

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