title: Salsolinol facilitates glutamatergic transmission to dopamine neurons in the posterior ventral tegmental area of rats.
abstract: Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA) partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D(1) receptors (D(1)Rs). In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D(1)Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs) and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D(1)R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D(1)Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol.
authors.affiliation: Department of Anesthesiology, Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Xie
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Ye
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D011810:Quinoxalines; D017447:Receptors, Dopamine D1; D000431:Ethanol; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C036617:salsolinol