Document Detail


Opioids in the nucleus accumbens stimulate ethanol intake.
MedLine Citation:
PMID:  19647755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nucleus accumbens (NAc) participates in the control of both motivation and addiction. To test the possibility that opioids in the NAc can cause rats to select ethanol in preference to food, Sprague-Dawley rats with ethanol, food, and water available, were injected with two doses each of morphine, the mu-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-Enkephalin (DAMGO), the delta-receptor agonist D-Ala-Gly-Phe-Met-NH2 (DALA), the k-receptor agonist (+/-)-trans-U-50488 methanesulfonate (U-50,488H), or the opioid antagonist naloxone methiodide (m-naloxone). As an anatomical control for drug reflux, injections were also made 2mm above the NAc. The main result was that morphine in the NAc significantly increased ethanol and food intake, whereas m-naloxone reduced ethanol intake without affecting food or water intake. Of the selective receptor agonists, DALA in the NAc increased ethanol intake in preference to food. This is in contrast to DAMGO, which stimulated food but not ethanol intake, and the k-agonist U-50,488H, which had no effect on intake. When injected in the anatomical control site 2mm dorsal to the NAc, the opioids had no effects on ethanol intake. These results demonstrate that ethanol intake produced by morphine in the NAc is driven in large part by the delta-receptor. In light of other studies showing ethanol intake to increase enkephalin expression in the NAc, the present finding of enkephalin-induced ethanol intake suggests the existence of a positive feedback loop that fosters alcohol abuse. Naltrexone therapy for alcohol abuse may then act, in part, in the NAc by blocking this opioid-triggered cycle of alcohol intake.
Authors:
Jessica R Barson; Ambrose J Carr; Jennifer E Soun; Nasim C Sobhani; Sarah F Leibowitz; Bartley G Hoebel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2009-08-06
Journal Detail:
Title:  Physiology & behavior     Volume:  98     ISSN:  1873-507X     ISO Abbreviation:  Physiol. Behav.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-18     Completed Date:  2009-12-09     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0151504     Medline TA:  Physiol Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
Administration, Oral
Alcohol Drinking / physiopathology*
Analgesics, Non-Narcotic / pharmacology
Analgesics, Opioid / metabolism*,  pharmacology
Animals
Central Nervous System Depressants / administration & dosage*
Conditioning, Operant / drug effects
Dose-Response Relationship, Drug
Eating / drug effects
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
Ethanol / administration & dosage*,  blood
Male
Morphine / pharmacology
Naloxone / pharmacology
Narcotic Antagonists / pharmacology
Narcotics / pharmacology
Nucleus Accumbens / drug effects,  metabolism*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
AA12882/AA/NIAAA NIH HHS; R01 DA021518/DA/NIDA NIH HHS; R01 DA021518-16A1/DA/NIDA NIH HHS; R01 DA021518-17/DA/NIDA NIH HHS; R01 DA021518-18/DA/NIDA NIH HHS; R01 DA021518-19/DA/NIDA NIH HHS; R01 MH043422/MH/NIMH NIH HHS; R01 MH043422-10/MH/NIMH NIH HHS; R01 MH043422-10S1/MH/NIMH NIH HHS; R01 MH043422-11A3/MH/NIMH NIH HHS; R01 MH043422-12/MH/NIMH NIH HHS; R01 MH043422-13/MH/NIMH NIH HHS; R01 MH043422-14/MH/NIMH NIH HHS; R01 MH043422-15/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 0/Analgesics, Opioid; 0/Central Nervous System Depressants; 0/Narcotic Antagonists; 0/Narcotics; 100929-53-1/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; 36B82AMQ7N/Naloxone; 3K9958V90M/Ethanol; 67198-13-4/3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; 76I7G6D29C/Morphine
Comments/Corrections

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