Document Detail

Central nervous system site of action for the respiratory depressant effect of diacetylmorphine (heroin) in the cat.
MedLine Citation:
PMID:  6313755     Owner:  NLM     Status:  MEDLINE    
The purpose of our study was to identify central nervous system sites involved in the respiratory depressant effect of drugs that stimulate opioid receptors. Diacetylmorphine (heroin) was administered into several cerebroventricular regions of chloralose-anesthetized cats, while monitoring pulmonary ventilation with a Fleisch pneumotachograph. Administration of heroin (17, 50, 150, and 450 micrograms) into the forebrain ventricles, which was restricted to these ventricles, resulted in no significant respiratory effects. In contrast, administration of heroin into either the fourth ventricle or the cisterna magna resulted in a significant (P less than 0.05) decrease in respiratory minute volume (VE). In the fourth ventricle this was because of a decrease in frequency (f) and in the cisterna magna, to a decrease in tidal volume (VT). Intravenous administration of heroin in the same dose-range produced a decrease in VE, which was primarily due to a decrease in f. Bilateral application of heroin (70 micrograms/side) to each of three ventral medullary surface sites (Mitchell's, Schlaefke's, and Loeschcke's areas) known to influence respiration elicited a decrease in VE only at Mitchell's area. This decrease was due to decreases in f and VT. The role of this site in the action of intravenously administered heroin was tested by topical application of naloxone to this area in animals with respiratory depression evoked by intravenous heroin. Bilateral application of naloxone (15 micrograms/side) to Mitchell's area restored breathing to normal. These results lead us to suggest that the site of heroin-induced respiratory depression is a specific area (Mitchell's area) on the ventral surface of the medulla.
A M Taveira da Silva; J D Souza; J A Quest; F D Pagani; J M Moerschbaecher; A Buller; P Hamosh; R A Gillis
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  72     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1983 Oct 
Date Detail:
Created Date:  1983-12-17     Completed Date:  1983-12-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1209-17     Citation Subset:  AIM; IM    
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MeSH Terms
Administration, Topical
Brain Chemistry / drug effects*
Depression, Chemical
Heroin / administration & dosage*,  pharmacology
Injections, Intravenous
Injections, Intraventricular
Lung Volume Measurements
Naloxone / administration & dosage,  pharmacology
Receptors, Opioid / physiology
Respiration / drug effects*
Time Factors
Grant Support
1-RO1-29562//PHS HHS; DA 02679/DA/NIDA NIH HHS
Reg. No./Substance:
0/Receptors, Opioid; 465-65-6/Naloxone; 561-27-3/Heroin

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