The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats

James Kasper; Rajiv Tikamdas; Myong Sang Kim; Kaley Macfadyen; Richard Aramini; Joseph Ladd; Sarah Bisceglia; Raymond Booth; Joanna Peris

doi:10.1016/j.ejphar.2013.09.008

The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats

James Kasper, Rajiv Tikamdas, Myong Sang Kim, Kaley Macfadyen, Richard Aramini, Joseph Ladd, Sarah Bisceglia, Raymond Booth, Joanna Peris

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Serotonin (5-HT) 5-HT_2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT_2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT_2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT₂ family receptor agonist, decreased both ethanol and vehicle responding while (-)-trans-PAT, a 5-HT_2C receptor agonist with 5-HT_2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT_2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (-)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT₂ family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.

Original language	English (US)
Pages (from-to)	98-104
Number of pages	7
Journal	European Journal of Pharmacology
Volume	718
Issue number	1-3
DOIs	https://doi.org/10.1016/j.ejphar.2013.09.008
State	Published - 2013
Externally published	Yes

Keywords

Alcohol deprivation
Alcoholism
Ethanol
Operant self-administration
Serotonin 2C receptor

ASJC Scopus subject areas

Pharmacology

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10.1016/j.ejphar.2013.09.008

Cite this

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title = "The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats",

abstract = "Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both ethanol and vehicle responding while (-)-trans-PAT, a 5-HT2C receptor agonist with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (-)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.",

keywords = "Alcohol deprivation, Alcoholism, Ethanol, Operant self-administration, Serotonin 2C receptor",

author = "James Kasper and Rajiv Tikamdas and Kim, {Myong Sang} and Kaley Macfadyen and Richard Aramini and Joseph Ladd and Sarah Bisceglia and Raymond Booth and Joanna Peris",

note = "Funding Information: These studies were funded by grants from the U.S. National Institutes of Health ( DA023928 , DA030989 , MH081193 ). U.S. National Institutes of Health did not participate in study design, experiments, writing, or the decision to publish. ",

year = "2013",

doi = "10.1016/j.ejphar.2013.09.008",

language = "English (US)",

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T1 - The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats

AU - Kasper, James

AU - Tikamdas, Rajiv

AU - Kim, Myong Sang

AU - Macfadyen, Kaley

AU - Aramini, Richard

AU - Ladd, Joseph

AU - Bisceglia, Sarah

AU - Booth, Raymond

AU - Peris, Joanna

N1 - Funding Information: These studies were funded by grants from the U.S. National Institutes of Health ( DA023928 , DA030989 , MH081193 ). U.S. National Institutes of Health did not participate in study design, experiments, writing, or the decision to publish.

PY - 2013

Y1 - 2013

N2 - Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both ethanol and vehicle responding while (-)-trans-PAT, a 5-HT2C receptor agonist with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (-)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.

AB - Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both ethanol and vehicle responding while (-)-trans-PAT, a 5-HT2C receptor agonist with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (-)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.

KW - Alcohol deprivation

KW - Alcoholism

KW - Ethanol

KW - Operant self-administration

KW - Serotonin 2C receptor

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The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats

Abstract

Keywords

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