Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors.
BACKGROUND
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.
Halberstadt
Adam L
AL
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, USA.
Buell
Mahalah R
MR
Masten
Virginia L
VL
Risbrough
Victoria B
VB
Geyer
Mark A
MA
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D035841:Behavioral Research / Q000295:instrumentation; D003010:Clorgyline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005106:Exploratory Behavior / Q000187:drug effects*; D006246:Harmaline / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D008732:Methoxydimethyltryptamines / Q000737:chemistry / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010363:Pattern Recognition, Automated; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology; D058829:Serotonin 5-HT1 Receptor Antagonists; D013997:Time Factors
D008732:Methoxydimethyltryptamines; D008996:Monoamine Oxidase Inhibitors; D014677:Pharmaceutical Vehicles; D010879:Piperazines; D010880:Piperidines; D011619:Psychotropic Drugs; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D058829:Serotonin 5-HT1 Receptor Antagonists; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D006246:Harmaline; D003010:Clorgyline