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Modification of the effects of 5-MeO-DMT on exploratory behavior in rats by MAOI

Started by Flux, May 01, 2017, 04:22:53 AM

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Halberstadt AL, Buell MR, Masten VL, Risbrough VB & Geyer MA, 2008, 'Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors', Psychopharmacology, vol. 201, no. 1, pp. 55-66, doi: 10.1007/s00213-008-1247-z,


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.