Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe),2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe),and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (.)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±} )-3,4-methylenedioxym ethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information.25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (.80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74.78% drug-appropriate responding in DOM-trained and MDMAtrained rats at doses that suppressed responding. 5-MeODALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25INBOMe, fully substituted for DOM, whereas only 25BNBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalBehavioural pharmacology
Volume28
Issue number5
DOIs
StatePublished - 19 May 2017

Fingerprint

Hallucinogens
Rodentia
Locomotion
2,5-Dimethoxy-4-Methylamphetamine
Pharmaceutical Preparations
1-(4-methylphenyl)propane-2-amine
2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine

Keywords

  • DOM
  • MDMA
  • drug discrimination
  • locomotor activity
  • mouse
  • novel hallucinogens
  • rat

Cite this

@article{2e3641bee2d94a3e9bd0955bf6f6f2a8,
title = "Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents",
abstract = "There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe),2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe),and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (.)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±} )-3,4-methylenedioxym ethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information.25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (.80{\%}) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67{\%} drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74.78{\%} drug-appropriate responding in DOM-trained and MDMAtrained rats at doses that suppressed responding. 5-MeODALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25INBOMe, fully substituted for DOM, whereas only 25BNBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.",
keywords = "DOM, MDMA, drug discrimination, locomotor activity, mouse, novel hallucinogens, rat",
author = "Gatch, {Michael B.} and Dolan, {Sean B.} and Forster, {Michael J.}",
year = "2017",
month = "5",
day = "19",
doi = "10.1097/FBP.0000000000000309",
language = "English",
volume = "28",
pages = "375--385",
journal = "Behavioural Pharmacology",
issn = "0955-8810",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "5",

}

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents. / Gatch, Michael B.; Dolan, Sean B.; Forster, Michael J.

In: Behavioural pharmacology, Vol. 28, No. 5, 19.05.2017, p. 375-385.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents

AU - Gatch, Michael B.

AU - Dolan, Sean B.

AU - Forster, Michael J.

PY - 2017/5/19

Y1 - 2017/5/19

N2 - There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe),2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe),and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (.)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±} )-3,4-methylenedioxym ethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information.25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (.80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74.78% drug-appropriate responding in DOM-trained and MDMAtrained rats at doses that suppressed responding. 5-MeODALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25INBOMe, fully substituted for DOM, whereas only 25BNBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

AB - There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe),2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe),and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (.)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±} )-3,4-methylenedioxym ethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information.25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (.80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74.78% drug-appropriate responding in DOM-trained and MDMAtrained rats at doses that suppressed responding. 5-MeODALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25INBOMe, fully substituted for DOM, whereas only 25BNBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

KW - DOM

KW - MDMA

KW - drug discrimination

KW - locomotor activity

KW - mouse

KW - novel hallucinogens

KW - rat

UR - http://www.scopus.com/inward/record.url?scp=85019599358&partnerID=8YFLogxK

U2 - 10.1097/FBP.0000000000000309

DO - 10.1097/FBP.0000000000000309

M3 - Article

C2 - 28537942

AN - SCOPUS:85019599358

VL - 28

SP - 375

EP - 385

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

SN - 0955-8810

IS - 5

ER -