Alpha 1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice.
Previous studies have indicated excitatory adrenergic effects on midbrain dopamine systems. To investigate the cellular mechanisms, intracellular recordings were made from neurons in perfused, oxygenated slices of male rat midbrain. Electrophysiological and pharmacological parameters were used to identify cells as principal (presumably dopaminergic) neurons as opposed to secondary (presumably GABAergic) neurons in the substantia nigra zona compacta and the ventral tegmental area. Noradrenalin (10-100 microM) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine D2 receptor antagonist, completely blocked noradrenalin-induced hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58% of all principal neurons and had no effect in 42%; this effect was mimicked by the alpha-adrenergic agonist phenylephrine (10-30 microM) which depolarized 43 of 72 cells. The alpha 1 receptor antagonist prazosin (30-100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas alpha 2- and beta-adrenergic agents had no effect. In voltage clamp, phenylephrine evoked an inward current (at -60 mV) and reduced cord conductance by 0.81 +/- 0.14 nS (n = 4). Inward current evoked by phenylephrine became outward at -96 +/- 8 mV, which is near the membrane reversal potential for potassium as predicted by the Nernst equation. Phenylephrine also depolarized secondary cells and increased the frequency of spontaneous GABAA receptor-mediated postsynaptic potentials recorded in both principal and secondary cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Grenhoff
J
J
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201, USA.
North
R A
RA
Johnson
S W
SW
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D004298:Dopamine; D001640:Bicuculline