title: The cannabinoid CB2 receptor is necessary for nicotine-conditioned place preference, but not other behavioral effects of nicotine in mice.
abstract: BACKGROUND
  Whereas cannabinoid CB1 receptors have long been known to contribute to the rewarding effects and dependence liability of many drugs of abuse, recent studies have implicated the involvement of cannabinoid CB2 receptors.
  
  
  OBJECTIVE
  Here, we evaluated the role of CB2 receptors in the rewarding properties of nicotine, as assessed in the conditioned place preference (CPP) paradigm and mecamylamine-precipitated withdrawal in nicotine dependent mice.
  
  
  METHODS
  Using complementary pharmacological and genetic approaches, we investigated the involvement of CB2 receptors in nicotine- and cocaine-induced CPP in mice and mecamylamine-precipitated withdrawal in nicotine-dependent mice. We also determined whether deletion of CB2 receptors affects nicotine-induced hypothermia and hypoalgesia.
  
  
  RESULTS
  Nicotine-induced (0.5 mg/kg) CPP was completely blocked by selective CB2 antagonist, SR144528 (3 mg/kg) in wild-type mice, and was absent in CB2 (-/-) mice. Conversely, the CB2 receptor agonist, O-1966 (1, 3, 5, 10, 20 mg/kg) given in combination with a subthreshold dose of nicotine (0.1 mg/kg) elicited a place preference. In contrast, O-1966 (20 mg/kg) blocked cocaine (10 mg/kg)-induced CPP in wild type mice, while CB2 (-/-) mice showed unaltered cocaine CPP. CB2 (+/+) and (-/-) nicotine-dependent mice showed almost identical precipitated withdrawal responses and deletion of CB2 receptor did not alter acute somatic effects of nicotine.
  
  
  CONCLUSIONS
  Collectively, these results indicate that CB2 receptors are required for nicotine-induced CPP in the mouse, while it is not involved in nicotine withdrawal or acute effects of nicotine. Moreover, these results suggest that CB2 receptors play opposing roles in nicotine- and cocaine-induced CPP.
authors: Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA, bogna.ignatowska@gmail.com.
authors: Bogna M
authors: BM
authors: Ignatowska-Jankowska
authors: Pretal P
authors: PP
authors: Muldoon
authors: Aron H
authors: AH
authors: Lichtman
authors: M Imad
authors: MI
authors: Damaj
mesh_terms: D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D003511:Cyclohexanols; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014029:Tobacco Use Disorder / Q000378:metabolism
chemical_list: C531961:1-(4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl)-3-methylcyclohexanol; D000840:Anisoles; D003511:Cyclohexanols; D043885:Receptor, Cannabinoid, CB2; D008464:Mecamylamine; D009538:Nicotine; D003042:Cocaine
references: J Pharmacol Exp Ther. 2007 Jul;322(1):399-407
references: 17446302
references: Psychopharmacology (Berl). 2006 Mar;184(3-4):456-63
references: 16463055
references: Neuropharmacology. 2011 Feb-Mar;60(2-3):244-51
references: 20849866
references: Nature. 1993 Sep 2;365(6441):61-5
references: 7689702
references: Eur J Neurosci. 1999 Aug;11(8):2731-6
references: 10457169
references: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10819-24
references: 12136125
references: Biochem Biophys Res Commun. 1995 Oct 4;215(1):89-97
references: 7575630
references: J Neurosci Res. 1998 Feb 1;51(3):391-402
references: 9486774
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10821-6
references: 15247426
references: Psychopharmacology (Berl). 1999 Mar;143(1):39-46
references: 10227078
references: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9371-6
references: 11470906
references: Neuropharmacology. 2012 Sep;63(3):434-40
references: 22561751
references: J Pharmacol Exp Ther. 2008 Nov;327(2):482-90
references: 18725543
references: Behav Brain Res. 2011 Feb 2;217(1):111-6
references: 20937331
references: Pharmacol Rep. 2006 Nov-Dec;58(6):806-19
references: 17220538
references: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5300-5
references: 11320258
references: Behav Pharmacol. 2002 Sep;13(5-6):451-63
references: 12394421
references: J Cereb Blood Flow Metab. 2007 Jul;27(7):1387-96
references: 17245417
references: Neuropsychopharmacology. 2005 Jan;30(1):145-55
references: 15292905
references: Life Sci. 2013 Mar 19;92(8-9):458-62
references: 22705310
references: J Pharmacol Exp Ther. 2008 Apr;325(1):302-12
references: 18184829
references: Pharmacol Biochem Behav. 2005 Jun;81(2):387-95
references: 15935455
references: J Neurosci. 2007 Nov 14;27(46):12484-8
references: 18003826
references: J Pharmacol Exp Ther. 2013 Jan;344(1):207-17
references: 23115221
references: J Pharmacol Exp Ther. 2003 Nov;307(2):526-34
references: 12970387
references: Nat Rev Neurosci. 2010 Jun;11(6):389-401
references: 20485364
references: Nature. 1996 Nov 7;384(6604):83-7
references: 8900284
references: Psychopharmacology (Berl). 2000 Dec;153(1):31-43
references: 11255927
references: J Pharmacol Exp Ther. 2002 May;301(2):679-89
references: 11961073
references: Int J Neuropsychopharmacol. 2008 Nov;11(7):905-23
references: 18377702
references: Psychopharmacology (Berl). 1995 Jan;117(1):2-10; discussion 14-20
references: 7724697
references: Br J Pharmacol. 2010 Jun;160(3):467-79
references: 20590558
references: Science. 2005 Oct 14;310(5746):329-32
references: 16224028
references: Addict Biol. 2012 Jan;17(1):47-61
references: 21521420
references: Pharmacol Biochem Behav. 2005 Jun;81(2):381-6
references: 15925402
references: Neuroreport. 2004 Sep 15;15(13):2139-43
references: 15486497
references: Neuropsychiatr Dis Treat. 2007 Dec;3(6):711-21
references: 19300605
references: N Engl J Med. 2010 Jun 17;362(24):2295-303
references: 20554984
references: Nature. 1996 Feb 15;379(6566):606-12
references: 8628395
references: Neuropsychopharmacology. 2011 Oct;36(11):2339-48
references: 21796100
references: Br J Pharmacol. 2008 May;154(2):369-83
references: 18414385
references: Eur J Neurosci. 2000 Nov;12(11):4038-46
references: 11069600
references: Behav Brain Res. 1999 Oct;104(1-2):141-6
references: 11125733
references: Biochem Pharmacol. 1995 Jun 29;50(1):83-90
references: 7605349
references: Science. 1992 Dec 18;258(5090):1946-9
references: 1470919
references: Neuropharmacology. 2012 Sep;63(4):514-23
references: 22579668
references: Br J Pharmacol. 2007 Nov;152(5):583-93
references: 17641667
references: Psychopharmacology (Berl). 2006 Mar;184(3-4):339-44
references: 16416156
references: Psychopharmacology (Berl). 1998 Feb;135(4):324-32
references: 9539255
references: Br J Pharmacol. 2010 Aug;160(7):1773-84
references: 20649579
references: Nat Neurosci. 2011 Jul 24;14(9):1160-6
references: 21785434
references: Addict Biol. 2008 Jun;13(2):239-52
references: 18482433
references: Drug Metab Dispos. 1984 Nov-Dec;12(6):725-31
references: 6150822
references: J Pharmacol Exp Ther. 2007 Jan;320(1):250-7
references: 17021260
references: PLoS One. 2012;7(1):e29900
references: 22291896
references: Pharmacol Res. 2009 Aug;60(2):77-84
references: 19559360
references: PLoS One. 2008 Feb 20;3(2):e1640
references: 18286196
references: J Addict Res Ther. 2011 Oct 20;S1(2):
references: 22493758
references: Neuropsychopharmacology. 2012 Jun;37(7):1749-63
references: 22414816
references: Nat Neurosci. 2000 Nov;3(11):1073-4
references: 11036260
references: Clin Pharmacol Ther. 2008 Apr;83(4):531-41
references: 18305452
references: J Neurosci. 2012 Mar 21;32(12):4004-16
references: 22442067
references: Ann N Y Acad Sci. 2006 Aug;1074:514-36
references: 17105950
references: J Pharmacol Exp Ther. 2008 Aug;326(2):483-92
references: 18451315
references: Brain Res. 2006 Feb 3;1071(1):10-23
references: 16472786
references: J Pharmacol Exp Ther. 1999 Oct;291(1):390-8
references: 10490929
references: Psychopharmacology (Berl). 2013 Aug;228(3):419-26
references: 23503685
references: Curr Opin Pharmacol. 2009 Feb;9(1):65-73
references: 19162544
references: Brain Res. 2012 Mar 20;1444:45-54
references: 22325096
references: J Leukoc Biol. 2005 Dec;78(6):1192-7
references: 16204639
references: Addict Biol. 2010 Jul;15(3):277-88
references: 20477753
references: Nature. 1990 Aug 9;346(6284):561-4
references: 2165569
references: Trends Neurosci. 2006 Apr;29(4):225-32
references: 16483675