Document Detail


The role of peripheral Na(+) channels in triggering the central excitatory effects of intravenous cocaine.
MedLine Citation:
PMID:  16930444     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
While alterations in dopamine (DA) uptake appear to be a critical mechanism underlying locomotor and reinforcing effects of cocaine (COC), many centrally mediated physiological and affective effects of this drug are resistant to DA receptor blockade and are expressed more quickly following an intravenous (i.v.) injection than expected based on the dynamics of drug concentration in the brain. Because COC is also a potent local anesthetic, its rapid action on Na+ channels may be responsible for triggering these effects. We monitored temperatures in the nucleus accumbens, temporal muscle and skin together with conventional locomotion during a single i.v. injection of COC (1 mg/kg), procaine (PRO, 5 mg/kg; equipotential anesthetic dose), a short-acting local anesthetic drug that, like COC, interacts with Na+ channels, and cocaine methiodide (COC-MET, 1.31 mg/kg, equimolar dose), a quaternary COC derivative that is unable to cross the blood-brain barrier. In this way, we explored not only the importance of Na+ channels in general, but also the importance of central vs. peripheral Na+ channels specifically. COC induced locomotor activation, temperature increase in the brain and muscle, and a biphasic temperature fluctuation in skin. Though PRO did not induce locomotor activation, it mimicked, to a greater degree, the temperature effects of COC. Therefore, Na+ channels appear to be a key substrate for COC-induced temperature fluctuations in the brain and periphery. Similar to PRO, COC-MET had minimal effects on locomotion, but mimicked COC in its ability to increase brain and muscle temperature, and induce transient skin hypothermia. It appears therefore that COC's interaction with peripherally located Na+ channels triggers its central excitatory effects manifested by brain temperature increase, thereby playing a major role in drug sensing and possibly contributing to COC reinforcement.
Authors:
P Leon Brown; Eugene A Kiyatkin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  24     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-25     Completed Date:  2007-03-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  1182-92     Citation Subset:  IM    
Affiliation:
Cellular Neurobiology Branch, National Institute on Drug Abuse--Intramural Research Program, National Institutes of Health, DHHS, 333 Cassell Drive, Baltimore, MD 21224, USA.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, Local
Animals
Body Temperature / drug effects
Central Nervous System Stimulants* / administration & dosage,  pharmacology
Cocaine / administration & dosage,  analogs & derivatives*,  pharmacology
Drug Administration Routes
Male
Motor Activity / drug effects
Nucleus Accumbens / drug effects,  metabolism
Procaine* / administration & dosage,  pharmacology
Rats
Rats, Long-Evans
Sodium Channels / metabolism*
Chemical
Reg. No./Substance:
0/Anesthetics, Local; 0/Central Nervous System Stimulants; 0/Sodium Channels; 50-36-2/Cocaine; 59-46-1/Procaine; 5937-29-1/cocaine methiodide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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