Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors.
Adam L. Halberstadt, Mahalah R Buell, Virginia L Masten, Victoria B Risbrough, Mark A. Geyer
Psychopharmacology November 1, 2008 DOI: 10.1007/s00213-008-1247-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 5-MeO-DMT harmaline clorgyline (-)-deprenyl WAY-100635 MDL 11 939 |
| Dose | 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg), harmaline (0.1 mg/kg), clorgyline (0.3 mg/kg), WAY-100635 (1.0 mg/kg), MDL 11,939 (1.0 mg/kg) |
| Topics | 5-MeO-DMT Ayahuasca DMT |
| Keywords | Psychedelics Hallucinogens Harmaline Harmine Neuropharmacology Psychopharmacology Drug effects Mao inhibition Serotonin system Receptor mechanisms Animal behavior Locomotor activity Exploratory behavior Rat studies Rodent behavior Serotonin receptors 5-ht2a receptors 5-ht1a receptors Serotonergic system Receptor pharmacology |
| Citations | 46 |
| Key findings | Harmaline modifies the behavioral effects of 5-MeO-DMT in rats via MAO-A inhibition, and the resulting late hyperactivity is mediated by 5-HT2A receptors. |
Abstract
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. 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-HT(2A) 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. 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 MAO(A) inhibitor clorgyline, whereas the selective MAO(B) 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. The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by the inhibition of MAO(A). Furthermore, 5-HT(2A) receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAO(A) inhibitors.