Document Detail

The locus coeruleus nucleus as a site of action of the antinociceptive and behavioral effects of the nicotinic receptor agonist, epibatidine.
MedLine Citation:
PMID:  16460769     Owner:  NLM     Status:  MEDLINE    
The mechanisms and sites of action of epibatidine-induced antinociception and side effects are poorly understood. The present study tested the hypothesis that the locus coeruleus is a site of action of epibatidine. Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the locus coeruleus (LC), and after subcutaneous administration. Different groups of rats were injected with formalin into the rear paw after administration of either ACSF, epibatidine (0.01, 0.06, 0.12, and 0.3mug) into the locus coeruleus or epibatidine (2.5-5mug/kg) subcutaneously. Assessment of pain-related behavior was done by evaluating the incidence of favoring, lifting and licking of the injected paw in the different groups. Abnormal motor behavior was also recorded. Infusion of epibatidine into LC induced analgesia, which was reversed by prior infusion of mecamylamine into LC. Epibatidine into the locus coeruleus resulted in a significant lower pain score in the second phase of the formalin test compared to control rats and was as effective as subcutaneous epibatidine. The analgesic effects of epibatidine were regionally selective in that the administration of epibatidine outside the locus coeruleus area was not analgesic. The every tested dose of epibatidine administered into the locus coeruleus also produced freezing behavior immediately after injection, which was relatively short-lived compared to the analgesic effect. Freezing was inhibited by administration of mecamylamine into the LC. Together the results implicate the LC as a target for the analgesic effects of epibatidine.
Giovanni Cucchiaro; Nayla Chaijale; Kathryn G Commons
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-03
Journal Detail:
Title:  Neuropharmacology     Volume:  50     ISSN:  0028-3908     ISO Abbreviation:  Neuropharmacology     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-26     Completed Date:  2006-10-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  769-76     Citation Subset:  IM    
Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, USA.
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MeSH Terms
Analgesics / pharmacology
Bicyclo Compounds, Heterocyclic / pharmacology*
Dose-Response Relationship, Drug
Locus Coeruleus / drug effects*,  physiology
Motor Activity / drug effects*,  physiology
Nicotinic Agonists / pharmacology*
Pain Measurement / drug effects*,  methods
Pyridines / pharmacology*
Rats, Sprague-Dawley
Receptors, Nicotinic / physiology*
Reg. No./Substance:
0/Analgesics; 0/Bicyclo Compounds, Heterocyclic; 0/Nicotinic Agonists; 0/Pyridines; 0/Receptors, Nicotinic; 140111-52-0/epibatidine

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