TY - JOUR
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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U2 - 10.1016/j.ejphar.2013.09.008
DO - 10.1016/j.ejphar.2013.09.008
M3 - Article
C2 - 24041931
AN - SCOPUS:84887099989
SN - 0014-2999
VL - 718
SP - 98
EP - 104
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -