title: Dopamine depresses glutamatergic synaptic transmission in the rat parabrachial nucleus in vitro.
abstract: Nystatin-perforated patch recordings were made from rat parabrachial neurons in an in vitro slice preparation to examine the effect of dopamine on parabrachial cells and on excitatory synaptic transmission in this nucleus. In current clamp mode, dopamine reduced the amplitude of the evoked excitatory postsynaptic potential without significant change in membrane potential. In cells voltage-clamped at -65 mV, dopamine dose dependently and reversibly decreased evoked, pharmacologically isolated, excitatory postsynaptic currents with an EC50 of 31 microM. The reduction in excitatory postsynaptic current was accompanied by an increase in paired pulse ratio (a protocol used to detect presynaptic site of action) with no change in the holding current or in the decay of the evoked excitatory postsynaptic currents. In addition, dopamine altered neither postsynaptic (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate-induced currents, nor steady-state current voltage curves. Miniature excitatory postsynaptic current analysis revealed that dopamine caused a rightward shift of the frequency-distribution curve with no change in the amplitude-distribution curve, which is consistent with a presynaptic mechanism. The dopamine-induced attenuation of the excitatory postsynaptic current was almost completely blocked by the D1-like receptor antagonist SCH23390 (10 microM), although the D2-like antagonist sulpiride (10 microM) also partially blocked it. Combined application of both antagonists blocked all dopamine-induced synaptic effects. The synaptic effect of dopamine was mimicked by the D1-like agonist SKF38393 (50 microM), but the D2-1ike agonist quinpirole (50 microM) also had a small effect. Combined application of both agonists did not produce potentiated responses. Dopamine's effect on the excitatory postsynaptic current was independent of serotonin, GABA and adenosine receptors, but may have some interactions with adrenergic receptors. These results suggest that dopamine directly modulates excitatory synaptic events in the parabrachial nucleus predominantly via presynaptic D1-like receptors.
authors.affiliation: Neuroscience Research Group, University of Calgary, Alberta, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: S B
authors.initials: SB
authors.lastname: Kombian
authors.forename: J A
authors.initials: JA
authors.lastname: Zidichouski
authors.forename: Q J
authors.initials: QJ
authors.lastname: Pittman
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008803:Mianserin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010646:Phentolamine / Q000494:pharmacology; D011149:Pons / Q000187:drug effects / Q000502:physiology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D019257:Quinpirole; D008803:Mianserin; D018698:Glutamic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D013469:Sulpiride; D000241:Adenosine; D004298:Dopamine; D010646:Phentolamine