title: Low doses of the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, induces social facilitation in adolescent male rats.
abstract: Adolescents display high levels of interactions with peers relative to other age groups, with these interactions further enhanced by ethanol under some circumstances. Understanding of the neural mechanisms underlying these high levels of social interactions is important given that alcohol use is initiated during adolescence and adolescents tend to report drinking for social reasons. Given that ethanol's effects are associated in part with functional antagonism of the NMDA receptor system, the current experiment explored the role of NMDA antagonists for facilitating adolescent social behavior. Adolescent male Sprague-Dawley rats were challenged acutely with either the non-competitive NMDA antagonist, MK-801 (0.01, 0.03mg/kg), the NR2A antagonist, PEAQX (1.25, 3.75mg/kg) or the NR2B antagonist, ifenprodil (0.75, 2.25mg/kg) 30min prior to a 10-min social interaction test. All compounds generally increased overall social activity (i.e., sum of social investigation, contact behavior, and play), with ifenprodil also significantly enhancing play and social contact behaviors. Although the frequencies of peer-directed social behaviors were typically greater following administration with these NMDA antagonists, social preference, indexed via the number of crossovers to the side with the partner relative to crossovers away, was significantly reduced in MK-801 and PEAQX-treated rats. None of these changes were associated with concomitant alterations in overall locomotor activity under these test circumstances. These data support the suggestion that the increases in social interactions observed in adolescents following acute ethanol may be driven in part by NMDA receptor antagonism - particularly of the NR2B subunit - given that ifenprodil stimulated social behavior in a manner similar to that produced by low doses of ethanol.
authors: Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, United States. mmorale2@binghamton.edu
authors: Melissa
authors: M
authors: Morales
authors: Elena I
authors: EI
authors: Varlinskaya
authors: Linda P
authors: LP
authors: Spear
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012932:Social Facilitation
chemical_list: C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011810:Quinoxalines; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C010739:ifenprodil
references: Brain Res. 1997 Sep 12;768(1-2):30-6
references: 9369297
references: Science. 1989 Mar 31;243(4899):1721-4
references: 2467382
references: Alcohol Clin Exp Res. 2011 Jun;35(6):1149-59
references: 21352242
references: Neuropharmacology. 1995 Mar;34(3):347-55
references: 7630488
references: Behav Brain Res. 2008 Apr 9;188(2):398-405
references: 18242726
references: Eur J Pharmacol. 2000 Nov 10;408(1):41-9
references: 11070182
references: Alcohol. 2010 Feb;44(1):99-110
references: 20113878
references: Eur J Pharmacol. 1995 Apr 4;276(3):257-66
references: 7601211
references: Alcohol Clin Exp Res. 2005 Oct;29(10):1796-808
references: 16269909
references: Alcohol Clin Exp Res. 2002 Apr;26(4):449-56
references: 11981119
references: Depress Anxiety. 1997;5(1):29-33
references: 9250438
references: J Youth Adolesc. 1977 Sep;6(3):281-94
references: 24408457
references: Alcohol Clin Exp Res. 2002 Oct;26(10):1502-11
references: 12394283
references: Eur J Pharmacol. 1999 Mar 19;369(2):145-57
references: 10206172
references: Alcohol Clin Exp Res. 2007 Jul;31(7):1159-68
references: 17511750
references: J Neurosci. 2004 Oct 6;24(40):8885-95
references: 15470155
references: Alcohol Clin Exp Res. 2009 Jun;33(6):991-1000
references: 19302088
references: Pharmacol Biochem Behav. 2012 Jan;100(3):440-50
references: 22024161
references: Pharmacol Biochem Behav. 2010 Aug;96(2):228-35
references: 20478326
references: Neuropsychopharmacology. 2009 Nov;34(12):2560-73
references: 19657330
references: Behav Pharmacol. 1990;1(5):437-446
references: 11175428
references: Clin Psychol Rev. 2005 Nov;25(7):841-61
references: 16095785
references: Mol Pharmacol. 2006 Sep;70(3):1022-32
references: 16778008
references: Behav Brain Res. 2008 Aug 5;191(1):26-31
references: 18453008
references: Physiol Behav. 1995 May;57(5):843-7
references: 7610133