title: Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats.
abstract: Co-administration of the 5-HT1A serotonin receptor agonist (+/-)8-hydroxy-2-(N,N-di-n-propylamino)tetralin [(+/-)8-OH DPAT] enhances the discriminative stimulus effects of the classical hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats. In the present investigation, using Sprague-Dawley rats trained to discriminate DOM (1.0 mg/kg) from saline vehicle under a VI-15 s schedule of reinforcement, it was shown that the stimulus-enhancing actions of 8-OH DPAT are related more to its R(+)-isomer than to its S(-)-enantiomer, and that the (+/-)- and R(+)8-OH DPAT-induced effects are antagonized by the 5-HT1A receptor antagonist NAN-190. (+/-)8-OH DPAT and its isomers substitute in rats trained to discriminate the designer drug N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; methylenedioxymethamphetamine) from vehicle indicating some similarity of effect. On this basis, it was hypothesized that MDMA might be capable of enhancing the DOM stimulus. Co-administration of MDMA with low (i.e., 0.1 and 0.3 mg/kg) doses of DOM resulted in greater DOM-appropriate responding than engendered by administration of DOM alone. As such, the present findings are the first to demonstrate an MDMA-induced enhancing effect on the discriminative stimulus actions of a classical hallucinogen. The results also suggest that a 5-HT1A serotonin receptor mechanism might contribute to this phenomenon.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
authors.forename: Nantaka
authors.initials: N
authors.lastname: Khorana
authors.forename: Richard
authors.initials: R
authors.lastname: Young
authors.forename: Richard A
authors.initials: RA
authors.lastname: Glennon
mesh_terms: D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005795:Generalization, Stimulus / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D006213:Hallucinogens; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018817:N-Methyl-3,4-methylenedioxyamphetamine
references.citation: Eur J Pharmacol. 1988 Sep 23;154(3):339-41
references.pmid: 2976673
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2001 Jun;363(6):620-32
references.pmid: 11414657
references.citation: Neurosci Lett. 2006 Aug 14;404(1-2):122-6
references.pmid: 16759802
references.citation: J Pharmacol Exp Ther. 2006 May;317(2):838-49
references.pmid: 16434566
references.citation: NIDA Res Monogr. 1989;94:1-29
references.pmid: 2575223
references.citation: Life Sci. 1991;48(26):2493-8
references.pmid: 2046474
references.citation: Neuropsychopharmacology. 1998 Oct;19(4):241-51
references.pmid: 9718588
references.citation: Hum Psychopharmacol. 2001 Dec;16(8):589-598
references.pmid: 12404538
references.citation: J Med Chem. 1988 Oct;31(10):1968-71
references.pmid: 3172131
references.citation: Biochem Pharmacol. 1993 Jan 26;45(2):375-83
references.pmid: 8382063
references.citation: NIDA Res Monogr. 1991;(116):25-44
references.pmid: 1369672
references.citation: J Biol Chem. 1993 Aug 25;268(24):18200-4
references.pmid: 8394362
references.citation: Pharmacol Biochem Behav. 2000 Jul;66(3):483-8
references.pmid: 10899359
references.citation: Brain Res. 1990 Nov 5;532(1-2):191-6
references.pmid: 2282513
references.citation: Eur J Pharmacol. 1998 Jan 12;341(2-3):131-4
references.pmid: 9543229
references.citation: Eur J Pharmacol. 1998 Apr 10;346(2-3):181-8
references.pmid: 9652358
references.citation: Neuroscience. 2004;124(4):901-11
references.pmid: 15026130
references.citation: Pharmacol Biochem Behav. 1979 Apr;10(4):535-46
references.pmid: 37526
references.citation: Eur J Pharmacol. 2004 Mar 8;487(1-3):125-32
references.pmid: 15033384
references.citation: Drug Des Discov. 1993;9(3-4):287-97
references.pmid: 8400009
references.citation: Pharmacol Biochem Behav. 1985 Dec;23(6):937-41
references.pmid: 2934750
references.citation: Biol Psychiatry. 1982 Jul;17(7):807-14
references.pmid: 6126227
references.citation: Med Res Rev. 1986 Jan-Mar;6(1):99-130
references.pmid: 3512936
references.citation: Br J Pharmacol. 1991 Jun;103(2):1547-55
references.pmid: 1832068
references.citation: Drug Alcohol Depend. 2001 Dec 1;65(1):97-101
references.pmid: 11714594
references.citation: Eur J Pharmacol. 2000 May 12;396(1):1-8
references.pmid: 10822046
references.citation: Eur J Pharmacol. 1991 Feb 7;193(2):145-52
references.pmid: 1675609
references.citation: J Pharmacol Exp Ther. 1977 Apr;201(1):55-66
references.pmid: 15104
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1817-21
references.pmid: 1347426
references.citation: Mol Pharmacol. 1991 Jun;39(6):780-7
references.pmid: 1828859
references.citation: Pharmacol Biochem Behav. 1978 Dec;9(6):863-87
references.pmid: 34176
references.citation: Eur J Pharmacol. 1986 Dec 16;132(2-3):269-76
references.pmid: 2880735
references.citation: Neuropsychobiology. 2001 Jan;43(1):42-8
references.pmid: 11150898
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jun;29(5):648-57
references.pmid: 15908091
references.citation: Neuroscience. 2007 May 11;146(2):509-14
references.pmid: 17383105
references.citation: J Pharm Pharmacol. 2004 Oct;56(10):1267-74
references.pmid: 15482641
references.citation: Commun Psychopharmacol. 1980;4(6):501-6
references.pmid: 7297054
references.citation: Psychopharmacology (Berl). 2005 Oct;182(2):197-204
references.pmid: 16025319
references.citation: Pharmacol Biochem Behav. 1986 Jul;25(1):135-9
references.pmid: 2944129
references.citation: Pharmacol Biochem Behav. 1992 Dec;43(4):1099-106
references.pmid: 1361990
references.citation: Brain Res. 2006 Mar 10;1077(1):178-86
references.pmid: 16483555
references.citation: Eur J Neurosci. 2006 May;23(10):2669-76
references.pmid: 16817869
references.citation: Neuron. 1993 Sep;11(3):449-58
references.pmid: 8398139
references.citation: Pharmacol Biochem Behav. 1998 Feb;59(2):265-70
references.pmid: 9476968
references.citation: Drug Alcohol Depend. 2004 Jun 11;74(3):281-7
references.pmid: 15194206
references.citation: Neuropharmacology. 1997 Nov-Dec;36(11-12):1697-703
references.pmid: 9517441
references.citation: Behav Brain Res. 2004 Dec 6;155(2):275-82
references.pmid: 15364487
references.citation: Biochem Pharmacol. 1983 Apr 1;32(7):1267-73
references.pmid: 6573879
references.citation: NIDA Res Monogr. 1989;94:43-67
references.pmid: 2575229