Document Detail

Mu-opioid receptors are not involved in acute cocaine-induced locomotor activity nor in development of cocaine-induced behavioral sensitization in mice.
MedLine Citation:
PMID:  15257307     Owner:  NLM     Status:  MEDLINE    
Although mu-opioid receptors have been extensively investigated for their role in drug reinforcement, little is known about the contribution of these receptors to the acute and sensitized locomotor response to cocaine. In this study mu-opioid receptor involvement in acute cocaine-induced locomotor activity and in the development of cocaine-induced behavioral sensitization was evaluated using mu-opioid receptor knockout mice and chronic naltrexone (NTX) pretreatment as models. In addition, co-administration of the specific mu-opioid receptor antagonist CTOP with repeated saline or cocaine injections was used to establish the involvement of mu-opioid receptors in sensitization to the locomotor stimulant effects of cocaine. The acute locomotor response to cocaine (3, 10, 20, or 30 mg/kg i.p.) of mu-opioid receptor knockout or chronic NTX pretreated mice was not different from the cocaine response of their respective controls. With respect to cocaine-induced behavioral sensitization, induced by daily injections of 20 mg/kg cocaine for 11 subsequent days, mu-opioid receptor knockout mice developed behavioral sensitization to the locomotor stimulant effects of cocaine (challenge 10 mg/kg i.p.) comparable to wild-type littermates and the mu-opioid receptor antagonist CTOP did not affect cocaine-induced sensitization either. However, mice that were pretreated with NTX exhibited augmented cocaine-induced behavioral sensitization relative to placebo pretreated controls, which may be ascribed to increased delta-opioid receptor levels as has been described for chronic NTX pretreated mice. The present findings suggest that mu-opioid receptors are not required for the acute locomotor response to cocaine nor are they essential for the development of cocaine-induced behavioral sensitization.
Heidi M B Lesscher; Michiel Hordijk; Natalia P Bondar; Olga V Alekseyenko; J Peter H Burbach; Jan M van Ree; Mirjam A F M Gerrits
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  30     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-19     Completed Date:  2005-02-15     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  278-85     Citation Subset:  IM    
Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Stratenum, Universiteitsweg 100, Utrecht, The Netherlands.
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MeSH Terms
Behavior, Animal / drug effects*
Cocaine / pharmacology*
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / drug effects*
Naltrexone / pharmacology
Narcotic Antagonists / pharmacology
Receptors, Opioid, delta / drug effects,  metabolism
Receptors, Opioid, kappa / drug effects,  metabolism
Receptors, Opioid, mu / drug effects*
Somatostatin / analogs & derivatives*,  pharmacology
Stimulation, Chemical
Reg. No./Substance:
0/Narcotic Antagonists; 0/Receptors, Opioid, delta; 0/Receptors, Opioid, kappa; 0/Receptors, Opioid, mu; 103429-31-8/phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; 16590-41-3/Naltrexone; 50-36-2/Cocaine; 51110-01-1/Somatostatin

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