κ-Opioid receptor modulation of accumbal dopamine concentration during operant ethanol self-administration

• Published in: Neuropharmacology Vol. 51; no. 3; pp. 487 - 496
• Main Authors: Doyon, William M., Howard, Elaina C., Shippenberg, Toni S., Gonzales, Rueben A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2006
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology; Analgesics, Non-Narcotic - pharmacology; Animals; Area Under Curve; Behavior, Animal; Central Nervous System Depressants - administration & dosage; Conditioning, Operant - drug effects; Dopamine - metabolism; Dose-Response Relationship, Drug; Drinking Behavior - drug effects; Drug Interactions; Ethanol - administration & dosage; Ethanol self-administration; Male; Microdialysis; Microdialysis - methods; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Nor-binaltorphimine; Nucleus accumbens; Nucleus Accumbens - metabolism; Operant; Rats; Rats, Long-Evans; Receptors, Opioid, kappa - physiology; Self Administration - methods; Ethanol self-administration; Nucleus accumbens; Microdialysis; Nor-binaltorphimine; Operant
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2006.04.005

Our study examined ethanol self-administration and accumbal dopamine concentration during κ-opioid receptor (KOPr) blockade. Long-Evans rats were trained to respond for 20
min of access to 10% ethanol (with sucrose) over 7
days. Rats were injected s.c. with the long-acting KOPr antagonist, nor-binaltorphimine (NOR-BNI; 0 or 20
mg/kg) 15–20
h prior to testing. Microdialysis revealed a transient elevation in dopamine concentration within 5
min of ethanol access in controls. NOR-BNI-treated rats did not exhibit this response, but showed a latent increase in dopamine concentration at the end of the access period. The rise in dopamine levels correlated positively with dialysate ethanol concentration but not in controls. NOR-BNI did not alter dopamine levels in rats self-administering 10% sucrose. The transient dopamine response during ethanol acquisition in controls is consistent with previous results that were attributed to ethanol stimulus cues. The altered dopamine response to NOR-BNI during ethanol drinking suggests that KOPr blockade temporarily uncovered a pharmacological stimulation of dopamine release by ethanol. Despite these neurochemical changes, NOR-BNI did not alter operant responding or ethanol intake, suggesting that the KOPr is not involved in ethanol-reinforced behavior under the limited conditions we studied.