Document Detail

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.
MedLine Citation:
PMID:  14755004     Owner:  NLM     Status:  MEDLINE    
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.
Maia Terashvili; Hsiang-en Wu; Randy J Leitermann; Kuei-chun Hung; Andrew D Clithero; Emma T Schwasinger; Leon F Tseng
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-01-30
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  309     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-23     Completed Date:  2004-06-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  816-24     Citation Subset:  IM    
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
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MeSH Terms
Conditioning (Psychology) / drug effects*
Dynorphins / immunology,  pharmacology
Naltrexone / analogs & derivatives*,  pharmacology
Nucleus Accumbens / drug effects*,  physiology
Oligopeptides / pharmacology*
Receptors, Opioid, kappa / metabolism
Receptors, Opioid, mu / metabolism
Serum / metabolism
Somatostatin / analogs & derivatives*,  pharmacology
Space Perception / drug effects
Substantia Nigra / drug effects,  physiology
Ventral Tegmental Area / drug effects*,  physiology
Grant Support
Reg. No./Substance:
0/3-methoxynaltrexone; 0/Oligopeptides; 0/Receptors, Opioid, kappa; 0/Receptors, Opioid, mu; 0/endomorphin 1; 0/endomorphin 2; 103429-31-8/phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; 16590-41-3/Naltrexone; 51110-01-1/Somatostatin; 74913-18-1/Dynorphins

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