TY - JOUR
T1 - Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats
AU - Fantegrossi, W. E.
AU - Harrington, A. W.
AU - Kiessel, C. L.
AU - Eckler, J. R.
AU - Rabin, R. A.
AU - Winter, J. C.
AU - Coop, A.
AU - Rice, K. C.
AU - Woods, J. H.
N1 - Funding Information:
This research was supported by by USPHS grants DA 03385 (JRE, RAR, JCW), DA09161 and DA05923 (WEF and JHW), as well as by the College on Problems of Drug Dependence. The authors express their gratitude to the University of Michigan Undergraduate Research Opportunity Program, and for the expert technical assistance provided by the University of Michigan Unit for Laboratory Animal Medicine staff.
PY - 2006/1
Y1 - 2006/1
N2 - Few studies have examined the effects of 5-methoxy-N,N- diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT2A and 5-HT2C receptors, but much higher affinity for 5-HT1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT1A receptor.
AB - Few studies have examined the effects of 5-methoxy-N,N- diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT2A and 5-HT2C receptors, but much higher affinity for 5-HT1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT1A receptor.
KW - Drug-discrimination
KW - Hallucinogens
KW - Head twitch response
KW - Serotonin receptors
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U2 - 10.1016/j.pbb.2005.12.015
DO - 10.1016/j.pbb.2005.12.015
M3 - Article
C2 - 16460788
AN - SCOPUS:33644906908
VL - 83
SP - 122
EP - 129
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 1
ER -