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.
authors.affiliation: University of Florida, Department of Pharmacodynamics, Box 100487, 1600 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: James
authors.initials: J
authors.lastname: Kasper
authors.forename: Rajiv
authors.initials: R
authors.lastname: Tikamdas
authors.forename: Myong Sang
authors.initials: MS
authors.lastname: Kim
authors.forename: Kaley
authors.initials: K
authors.lastname: Macfadyen
authors.forename: Richard
authors.initials: R
authors.lastname: Aramini
authors.forename: Joseph
authors.initials: J
authors.lastname: Ladd
authors.forename: Sarah
authors.initials: S
authors.lastname: Bisceglia
authors.forename: Raymond
authors.initials: R
authors.lastname: Booth
authors.forename: Joanna
authors.initials: J
authors.lastname: Peris
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D005260:Female; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D012054:Reinforcement, Psychology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D013764:Tetrahydronaphthalenes; C084981:1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene
keywords: Alcohol deprivation; Alcoholism; Ethanol; Operant self-administration; Serotonin 2C receptor
references.citation: Pharmacol Biochem Behav. 2005 Jan;80(1):109-14
references.pmid: 15652386
references.citation: Addict Behav. 2004 Sep;29(7):1341-57
references.pmid: 15345269
references.citation: Proc Natl Acad Sci U S A. 1990 Feb;87(3):928-32
references.pmid: 2300586
references.citation: Neuropharmacology. 1997 Apr-May;36(4-5):609-20
references.pmid: 9225286
references.citation: J Neurochem. 2008 Jul;106(1):170-81
references.pmid: 18346201
references.citation: Neuropharmacology. 2013 Jul;70:112-21
references.pmid: 23353901
references.citation: Pharmacol Biochem Behav. 2008 Nov;91(1):176-80
references.pmid: 18692085
references.citation: Pharmacol Ther. 2004 Feb;101(2):131-81
references.pmid: 14761703
references.citation: Curr Top Behav Neurosci. 2012;11:1-24
references.pmid: 22016109
references.citation: Eur J Pharmacol. 2003 Nov 7;480(1-3):151-62
references.pmid: 14623358
references.citation: Tetrahedron Lett. 2009 Sep 9;50(36):5107-5109
references.pmid: 20161011
references.citation: J Physiol. 2009 Jan 15;587(1):49-60
references.pmid: 19029184
references.citation: Science. 1988 Jul 29;241(4865):558-64
references.pmid: 3399891
references.citation: Pharmacol Ther. 2002 Apr-May;94(1-2):137-56
references.pmid: 12191599
references.citation: Prog Brain Res. 2008;172:319-46
references.pmid: 18772040
references.citation: Pharmacol Biochem Behav. 2006 Nov;85(3):562-8
references.pmid: 17140644
references.citation: Brain Res. 2010 Jan 15;1310:142-53
references.pmid: 19944084
references.citation: Br J Pharmacol. 1999 Sep;128(1):13-20
references.pmid: 10498829
references.citation: Physiol Behav. 2005 Jan 31;84(1):53-63
references.pmid: 15642607
references.citation: Curr Top Behav Neurosci. 2013;13:355-77
references.pmid: 22371267
references.citation: Eur J Pharmacol. 2009 Aug 1;615(1-3):1-9
references.pmid: 19397907
references.citation: Addict Biol. 2006 Sep;11(3-4):270-88
references.pmid: 16961759
references.citation: J Neural Transm (Vienna). 2006 Sep;113(9):1305-21
references.pmid: 16465467
references.citation: Physiol Behav. 2005 Sep 15;86(1-2):1-4
references.pmid: 16129461
references.citation: J Appl Behav Anal. 2008 Summer;41(2):155-61
references.pmid: 18595280
references.citation: Pharmacol Biochem Behav. 2004 Nov;79(3):439-50
references.pmid: 15582015
references.citation: Pharmacol Biochem Behav. 2002 Apr;71(4):735-44
references.pmid: 11888565
references.citation: Psychopharmacology (Berl). 2005 Apr;179(1):262-70
references.pmid: 15717208
references.citation: J Pharmacol Exp Ther. 2002 Jul;302(1):328-36
references.pmid: 12065734
references.citation: Curr Top Behav Neurosci. 2013;13:403-32
references.pmid: 22389178