Opioids in the nucleus accumbens stimulate ethanol intake.
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.
Barson
Jessica R
JR
Department of Psychology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA.
Carr
Ambrose J
AJ
Soun
Jennifer E
JE
Sobhani
Nasim C
NC
Leibowitz
Sarah F
SF
Hoebel
Bartley G
BG
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000284:Administration, Oral; D000428:Alcohol Drinking / Q000503:physiopathology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D009294:Narcotics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D000431:Ethanol; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine