Salsolinol stimulates dopamine neurons in slices of posterior ventral tegmental area indirectly by activating μ-opioid receptors

Guiqin Xie, Lucia Hipólito, Wanhong Zuo, Ana Polache, Luis Granero, Krešimir Krnjević, Jiang Hong Ye

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Previous studies in vivo have shown that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse. Although opioid receptors, especially the μ-opioid receptors (MORs), may be involved, the cellular mechanisms mediating the effects of salsolinol have not been fully explored. In the current study, we used whole-cell patch-clamp recordings to examine the effects of salsolinol on dopamine neurons of the ventral tegmental area (VTA) in acute brain slices from Sprague-Dawley rats. Salsolinol (0.01-1 μM) dose-dependently and reversibly increased the ongoing firing of dopamine neurons; this effect was blocked by naltrexone, an antagonist of MORs, and gabazine, an antagonist of GABA A receptors. We further showed that salsolinol reduced the frequency without altering the amplitude of spontaneous GABA A receptor-mediated inhibitory postsynaptic currents in dopamine neurons. The salsolinol-induced reduction was blocked by both naltrexone and [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin, an agonist of MORs. Thus, salsolinol excites VTA-dopamine neurons indirectly by activating MORs, which inhibit GABA neurons in the VTA. This form of disinhibition seems to be a novel mechanism underlying the effects of salsolinol.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume341
Issue number1
DOIs
StatePublished - Apr 1 2012

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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