title: Differential conditioned place preference responses to endomorphin-1 and endomorphin-2 microinjected into the posterior nucleus accumbens shell and ventral tegmental area in the rat.
abstract: An unbiased conditioned place preference (CPP) paradigm was used to evaluate the reward effects of endogenous mu-opioid receptor ligands endomorphin-1 (EM-1) and endomorphin-2 (EM-2) from the mesolimbic posterior nucleus accumbens (Acb) shell and the ventral tegmental area (VTA) in CD rats. EM-1 (1.6-8.1 nmol) microinjected into posterior Acb shell produced CPP, whereas EM-2 (8.7-17.5 nmol) given into the same Acb shell produced conditioned place aversion (CPA). EM-1 (1.6-16.3 nmol) microinjected into the VTA produced CPP, whereas EM-2 (8.7 and 17.5 nmol) given into the same VTA site did not produce any effect, but at a high dose (35 nmol) produced CPP. EM-1 (3.3 nmol) or EM-2 (17.5 nmol) microinjected into the nigrostriatal substantia nigra was not significantly different from vehicle-injected groups. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) at 94.13 pmol or 3-methoxynaltrexone at 0.64 pmol microinjected into the posterior Acb shell blocked EM-1-induced CPP and EM-2-induced CPA. At a higher dose, CTOP (941.3 pmol) and 3-methoxynaltrexone (6.4 pmol) produced CPA and CPP, respectively. Coadministration with antiserum against dynorphin A(1-17) (Dyn) (10 microg) microinjected into the posterior Acb shell blocked EM-2-induced CPA. However, it did not affect EM-1-induced CPP. It is concluded that EM-1 and EM-2 produce site-dependent CPP and CPA, respectively, by stimulation of different subtypes of mu-opioid-receptors; stimulation of one subtype of mu-opioid-receptor at the posterior Acb shell and VTA by EM-1 induces CPP, whereas stimulation of another subtype of mu-opioid receptor at the posterior Acb shell, but not the VTA, by EM-2 induces the release of Dyn to produce CPA.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Maia
authors.initials: M
authors.lastname: Terashvili
authors.forename: Hsiang-en
authors.initials: HE
authors.lastname: Wu
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Leitermann
authors.forename: Kuei-chun
authors.initials: KC
authors.lastname: Hung
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Clithero
authors.forename: Emma T
authors.initials: ET
authors.lastname: Schwasinger
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004399:Dynorphins / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: C107547:3-methoxynaltrexone; D009842:Oligopeptides; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C105294:endomorphin 2; D013004:Somatostatin; D009271:Naltrexone; D004399:Dynorphins