Salsolinol stimulates dopamine neurons in slices of posterior ventral tegmental area indirectly by activating μ-opioid receptors.
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.
Department of Anesthesiology, Pharmacology, and Physiology, UMDNJ, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Guiqin
G
Xie
Lucia
L
Hipólito
Wanhong
W
Zuo
Ana
A
Polache
Luis
L
Granero
Kresimir
K
Krnjevic
Jiang-Hong
JH
Ye
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D007546:Isoquinolines; D017450:Receptors, Opioid, mu; C036617:salsolinol