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

Jul 8, 2008Psychopharmacology

How enzymes that break down brain chemicals change the effects of 5-MeO-DMT on rats' exploratory behavior

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Abstract

5-MeO-DMT at doses of 0.01, 0.1, and 1.0 mg/kg decreased locomotor activity and investigatory behavior in rats.

The combination of 1.0 mg/kg 5-MeO-DMT and 0.1 mg/kg harmaline resulted in biphasic locomotor effects, initially decreasing activity followed by an increase over time.
The biphasic effect was also observed with the selective MAO(A) inhibitor clorgyline, while the selective MAO(B) inhibitor (-)-deprenyl did not produce similar effects.
Late hyperactivity caused by 1.0 mg/kg 5-MeO-DMT with clorgyline was blocked by the 5-HT(2A) antagonist MDL 11,939.
Pretreatment with the 5-HT(1A) antagonist WAY-100635 did not affect the early hypoactivity or the late hyperactivity linked to 5-MeO-DMT.

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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-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.

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 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.

CONCLUSIONS: 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.

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

Abstract

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