Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure
| Autor: | Sara R. Jones, Jamie H. Rose, Björn Steiniger-Brach, Anushree N. Karkhanis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Dopamine Narcotic Antagonists C57BL/6 Dynorphin Pharmacology release Naltrexone Nucleus Accumbens mouse voltammetry partial agonist dynorphin dopamine alcohol lcsh:Chemistry Mice 0302 clinical medicine lcsh:QH301-705.5 Spectroscopy Chemistry General Medicine Computer Science Applications medicine.drug Agonist medicine.medical_specialty medicine.drug_class Nucleus accumbens Partial agonist Catalysis Article Inorganic Chemistry 03 medical and health sciences Internal medicine medicine Animals Physical and Theoretical Chemistry Molecular Biology Nalmefene Ethanol Receptors Opioid kappa Organic Chemistry Central Nervous System Depressants 030227 psychiatry Mice Inbred C57BL Endocrinology lcsh:Biology (General) lcsh:QD1-999 Opioid 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 17, Iss 8, p 1216 (2016) International Journal of Molecular Sciences; Volume 17; Issue 8; Pages: 1216 |
| ISSN: | 1422-0067 |
| Popis: | The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc) κ opioid receptors (KOR) in chronic intermittent ethanol (CIE) exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs. |
| Databáze: | OpenAIRE |
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