title: Synergistic activity between the delta-opioid agonist SNC80 and amphetamine occurs via a glutamatergic NMDA-receptor dependent mechanism.
abstract: Glutamate is known to cause the release of dopamine through a Ca(2+)-sensitive mechanism that involves activation of NMDA ionotropic glutamate receptors. In the current study, we tested the hypothesis that the delta opioid agonist SNC80 acts indirectly, via the glutamatergic system, to enhance both amphetamine-stimulated dopamine efflux from striatal preparations and amphetamine-stimulated locomotor activity. SNC80 increased extracellular glutamate content, which was accompanied by a concurrent decrease in GABA levels. Inhibition of NMDA signaling with the selective antagonist MK801 blocked the enhancement of both amphetamine-induced dopamine efflux and hyperlocomotion observed with SNC80 pretreatment. Addition of exogenous glutamate also potentiated amphetamine-stimulated dopamine efflux in a Mg(2+)- and MK801-sensitive manner. After removal of Mg(2+) to relieve the ion conductance inhibition of NMDA receptors, SNC80 both elicited dopamine release alone and produced a greater enhancement of amphetamine-evoked dopamine efflux. The action of SNC80 to enhance amphetamine-evoked dopamine efflux was mimicked by the GABA(B) antagonist 2-hydroxysaclofen. These cumulative findings suggest SNC80 modulates amphetamine-stimulated dopamine efflux through an intra-striatal mechanism involving inhibition of GABA transmission leading to the local release of glutamate followed by subsequent activation of NMDA receptors.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Bosse
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Jutkiewicz
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Schultz-Kuszak
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Mabrouk
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Kennedy
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Gnegy
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: jtraynor@umich.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D001549:Benzamides; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D000661:Amphetamine; D004298:Dopamine
keywords: Amphetamine; Delta opioid receptor; Dopamine; GABA; Glutamate; SNC80
references.citation: J Pharmacol Exp Ther. 2009 Apr;329(1):290-6
references.pmid: 19168708
references.citation: Exp Neurol. 2012 Aug;236(2):339-50
references.pmid: 22575599
references.citation: Psychopharmacology (Berl). 1996 Apr;124(3):211-8
references.pmid: 8740041
references.citation: Synapse. 1996 Oct;24(2):135-46
references.pmid: 8890455
references.citation: J Neurochem. 2008 Dec;107(6):1647-59
references.pmid: 19094058
references.citation: Eur J Pharmacol. 1996 Mar 18;298(3):207-16
references.pmid: 8846818
references.citation: J Pharmacol Exp Ther. 1998 Feb;284(2):592-8
references.pmid: 9454802
references.citation: Behav Pharmacol. 1993 Dec;4(6):652-659
references.pmid: 11224234
references.citation: Brain Res. 1990 Jun 4;518(1-2):55-60
references.pmid: 1975217
references.citation: Brain Res. 1987 Dec 15;436(2):234-9
references.pmid: 2829990
references.citation: J Biol Chem. 1988 Dec 15;263(35):18873-9
references.pmid: 3058689
references.citation: Neuroscience. 2009 Dec 1;164(2):360-9
references.pmid: 19729051
references.citation: J Neurochem. 1991 Jan;56(1):81-5
references.pmid: 1824785
references.citation: Brain Res Bull. 1992 Aug;29(2):247-54
references.pmid: 1356069
references.citation: Brain Res. 1984 Oct 8;311(2):392-6
references.pmid: 6388730
references.citation: Synapse. 1998 Oct;30(2):227-35
references.pmid: 9723793
references.citation: Prog Brain Res. 1998;116:371-83
references.pmid: 9932389
references.citation: Neuroscience. 1999;93(4):1359-67
references.pmid: 10501460
references.citation: Eur J Pharmacol. 1997 Jul 16;331(1):1-8
references.pmid: 9274922
references.citation: Brain Res. 1992 Oct 30;594(2):327-30
references.pmid: 1360323
references.citation: Eur J Pharmacol. 2006 Feb 17;532(1-2):81-7
references.pmid: 16464448
references.citation: Synapse. 1992 May;11(1):47-57
references.pmid: 1318584
references.citation: Behav Pharmacol. 1998 Feb;9(1):9-14
references.pmid: 9832943
references.citation: Trends Neurosci. 1990 Jul;13(7):272-6
references.pmid: 1695402
references.citation: Brain Res. 2000 Apr 10;861(2):296-304
references.pmid: 10760491
references.citation: Life Sci. 1983;33 Suppl 1:73-6
references.pmid: 6664248
references.citation: Neuropharmacology. 1995 Mar;34(3):303-8
references.pmid: 7630485
references.citation: Nat Rev Neurosci. 2009 Aug;10(8):561-72
references.pmid: 19571793
references.citation: Electrophoresis. 2001 Oct;22(17):3668-76
references.pmid: 11699904
references.citation: J Pharmacol Exp Ther. 1998 Jul;286(1):362-75
references.pmid: 9655881
references.citation: Eur J Neurosci. 2004 Nov;20(10):2629-38
references.pmid: 15548206
references.citation: J Neurochem. 1991 Sep;57(3):819-22
references.pmid: 1650394
references.citation: J Pharmacol Exp Ther. 1999 Sep;290(3):1157-64
references.pmid: 10454490
references.citation: Eur J Pharmacol. 1992 Aug 25;219(2):345-6
references.pmid: 1425962
references.citation: J Neurochem. 1979 May;32(5):1539-45
references.pmid: 438822
references.citation: J Pharmacol Exp Ther. 2008 Feb;324(2):714-24
references.pmid: 17986650
references.citation: Anal Chem. 2012 Jan 3;84(1):412-9
references.pmid: 22118158
references.citation: Neuropharmacology. 2008 Oct;55(5):755-62
references.pmid: 18602932
references.citation: J Neurochem. 1997 Feb;68(2):517-24
references.pmid: 9003036
references.citation: J Pharmacol Exp Ther. 1992 Aug;262(2):638-45
references.pmid: 1323656
references.citation: Eur J Pharmacol. 1995 Jun 23;280(1):55-61
references.pmid: 7498254
references.citation: Brain Res. 1995 Oct 30;697(1-2):76-82
references.pmid: 8593597
references.citation: Psychopharmacology (Berl). 1998 Nov;140(2):217-24
references.pmid: 9860113
references.citation: J Pharmacol Exp Ther. 1992 Mar;260(3):1145-51
references.pmid: 1372049
references.citation: Eur J Pharmacol. 1993 Nov 9;249(2):167-77
references.pmid: 8287898
references.citation: Brain Res. 1996 Nov 11;739(1-2):169-81
references.pmid: 8955937
references.citation: J Neurochem. 1999 Sep;73(3):1058-65
references.pmid: 10461895
references.citation: J Pharmacol Exp Ther. 2005 Mar;312(3):1314-20
references.pmid: 15574687
references.citation: J Neurochem. 1990 Nov;55(5):1734-40
references.pmid: 1976759
references.citation: J Neurosci. 1992 Jan;12(1):356-61
references.pmid: 1309576
references.citation: J Pharmacol Exp Ther. 1991 Apr;257(1):262-70
references.pmid: 1673475
references.citation: Brain Res. 1990 Sep 17;527(2):266-79
references.pmid: 1701338
references.citation: Eur J Pharmacol. 2009 Feb 14;604(1-3):58-65
references.pmid: 19133255
references.citation: J Biol Chem. 1988 Jul 5;263(19):9292-7
references.pmid: 2897966
references.citation: J Neurosci. 1998 Mar 1;18(5):1923-33
references.pmid: 9465017
references.citation: Eur J Pharmacol. 1995 Sep 15;284(1-2):83-91
references.pmid: 8549640
references.citation: Regul Pept. 1984 Mar;8(2):105-15
references.pmid: 6328585
references.citation: Eur J Pharmacol. 1994 Mar 3;253(3):R9-11
references.pmid: 8200414
references.citation: Am J Psychiatry. 2005 Aug;162(8):1403-13
references.pmid: 16055761
references.citation: Brain Res. 1994 Nov 21;664(1-2):231-6
references.pmid: 7895034