Abstract:
RATIONALE:Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. OBJECTIVE:The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). METHODS:Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. RESULTS:MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. CONCLUSIONS:The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Carbonaro TM,Eshleman AJ,Forster MJ,Cheng K,Rice KC,Gatch MBdoi
10.1007/s00213-014-3658-3subject
Has Abstractpub_date
2015-01-01 00:00:00pages
275-84issue
1eissn
0033-3158issn
1432-2072journal_volume
232pub_type
杂志文章abstract:RATIONALE:Training in research ethics is crucial for psychiatric investigators. Addressing ethical dimensions of human subjects research requires knowledge about the rules and norms governing research; sensitivity to ethical implications of actions; and skills in ethics problem solving. Investigators in training who ar...
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journal_title:Psychopharmacology
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2010-01-01 00:00:00
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更新日期:2002-07-01 00:00:00
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更新日期:2006-08-01 00:00:00
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更新日期:2014-04-01 00:00:00
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更新日期:2015-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:1986-01-01 00:00:00
abstract:RATIONALE:Chronic stress and corticosterone have been shown to affect serotonin (5-HT) neurotransmission; however, the influence of stress on the activity of the dorsal raphe nucleus (DRN), the main source of 5-HT in the forebrain, is not well understood. In particular, it is unknown if and how stress modifies DRN 5-HT...
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更新日期:2018-12-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245428
更新日期:1992-01-01 00:00:00