title: Roles of opioid receptor subtypes in mediating alcohol-seeking induced by discrete cues and context.
abstract: The aim of this study was to assess the effects of selective blockade of the delta (DOP) or mu (MOP) opioid receptors on alcohol-seeking induced by discrete cues and context. In Experiment 1, rats were trained to self-administer alcohol in an environment with distinct sensory properties. After extinction in a different context with separate sensory properties, rats were tested for context-induced renewal in the original context following treatment with the DOP receptor antagonist naltrindole (0-15 mg/kg, i.p.) or the MOP receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) (0-3 microg/4 microL, i.c.v.). In Experiment 2, reinstatement was tested with the presentation of a discrete light + tone cue previously associated with alcohol delivery, following extinction without the cue. The effects of naltrindole (0-5 mg/kg, i.p.) or CTOP (0-3 microg/4 microL, i.c.v.) were assessed. For context-induced renewal, 7.5 mg/kg naltrindole reduced responding without affecting locomotor activity. Both doses of CTOP attenuated responding in the first 15 min of the renewal test session; however, total responses did not differ at the end of the session. For discrete-cue-induced reinstatement, 1 and 5 mg/kg naltrindole attenuated responding but CTOP had no effect. We conclude that whereas DOP receptors mediate alcohol-seeking induced by discrete cues and context, MOP receptors may play a modest role only in context-induced renewal. These findings point to a differential involvement of opioid receptor subtypes in the effects of different kinds of conditioned stimuli on alcohol-seeking and support a more prominent role for DOP receptors.
authors.affiliation: Department of Neuroscience, Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada. Peter_marinelli@camh.net
authors.forename: Peter W
authors.initials: PW
authors.lastname: Marinelli
authors.forename: Douglas
authors.initials: D
authors.lastname: Funk
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.forename: Walter
authors.initials: W
authors.lastname: Juzytsch
authors.forename: A D
authors.initials: AD
authors.lastname: Lê
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004777:Environment; D000431:Ethanol / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D012646:Self Administration; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D000431:Ethanol; D013004:Somatostatin; D009271:Naltrexone; C055382:naltrindole
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2046-50
references.pmid: 1347943
references.citation: J Pharmacol Exp Ther. 1993 Sep;266(3):1236-46
references.pmid: 7690399
references.citation: Neuropsychopharmacology. 2008 May;33(6):1402-12
references.pmid: 17653111
references.citation: Neuropharmacology. 2008 Oct;55(5):712-6
references.pmid: 18588903
references.citation: Alcohol. 2006 Feb;38(2):81-8
references.pmid: 16839854
references.citation: Neuropsychopharmacology. 2002 Dec;27(6):1006-15
references.pmid: 12464457
references.citation: Pharmacol Biochem Behav. 1998 Mar;59(3):627-35
references.pmid: 9512064
references.citation: Brain Res. 1993 Dec 10;630(1-2):330-2
references.pmid: 8118700
references.citation: Neuropsychopharmacology. 1999 Sep;21(3):435-44
references.pmid: 10457541
references.citation: Psychopharmacology (Berl). 1998 Jan;135(2):169-74
references.pmid: 9497022
references.citation: Psychopharmacology (Berl). 2003 Jul;168(1-2):222-228
references.pmid: 12719962
references.citation: Neuropsychopharmacology. 2002 Sep;27(3):391-9
references.pmid: 12225696
references.citation: Eur J Pharmacol. 1996 May 23;304(1-3):7-13
references.pmid: 8813578
references.citation: Behav Neurosci. 2002 Feb;116(1):169-73
references.pmid: 11895178
references.citation: Psychopharmacology (Berl). 2005 Sep;181(2):197-206
references.pmid: 15830224
references.citation: J Neurosci. 2007 Nov 14;27(46):12655-63
references.pmid: 18003845
references.citation: Pharmacol Biochem Behav. 1993 Jul;45(3):697-701
references.pmid: 8101382
references.citation: Psychopharmacology (Berl). 1991;103(4):467-72
references.pmid: 1648247
references.citation: Biol Psychiatry. 2007 Apr 15;61(8):979-89
references.pmid: 17098214
references.citation: Eur J Neurosci. 2007 Nov;26(10):2815-23
references.pmid: 18001278
references.citation: Psychopharmacology (Berl). 1995 Jul;120(2):177-85
references.pmid: 7480550
references.citation: Pharmacol Biochem Behav. 1995 Sep;52(1):153-9
references.pmid: 7501658
references.citation: Alcohol Clin Exp Res. 1999 Aug;23(8):1386-94
references.pmid: 10470982
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3233-43
references.pmid: 18640922
references.citation: Neuropsychopharmacology. 1999 May;20(5):471-9
references.pmid: 10192827
references.citation: J Neurosci. 2004 Nov 24;24(47):10726-30
references.pmid: 15564590
references.citation: Neuropsychopharmacology. 2005 Feb;30(2):296-309
references.pmid: 15483559
references.citation: Regul Pept. 1995 Oct 20;59(2):183-92
references.pmid: 8584753
references.citation: Psychopharmacology (Berl). 2003 Jul;168(1-2):208-215
references.pmid: 12664190
references.citation: J Pharmacol Exp Ther. 1989 Jan;248(1):73-80
references.pmid: 2563293
references.citation: Psychopharmacology (Berl). 1999 Nov;147(1):81-9
references.pmid: 10591872
references.citation: Brain Res. 1995 Aug 28;690(1):112-6
references.pmid: 7496796
references.citation: Alcohol Clin Exp Res. 2001 Jan;25(1):25-33
references.pmid: 11198711
references.citation: Behav Brain Res. 2006 Feb 15;167(1):150-5
references.pmid: 16256214
references.citation: Psychopharmacology (Berl). 2008 Oct;200(3):357-65
references.pmid: 18587561
references.citation: J Neurosci. 2002 Sep 15;22(18):7856-61
references.pmid: 12223538
references.citation: J Stud Alcohol. 1990 Nov;51(6):494-9
references.pmid: 2270057
references.citation: J Abnorm Psychol. 2000 Nov;109(4):738-42
references.pmid: 11195999
references.citation: Neuroscience. 2006;139(3):877-87
references.pmid: 16516392
references.citation: Eur J Pharmacol. 1988 Jan 27;146(1):185-6
references.pmid: 2832195