ALPHA(1)-ADRENERGIC EFFECTS ON DOPAMINE NEURONS RECORDED INTRACELLULARLY IN THE RAT MIDBRAIN SLICE

被引:99
作者
GRENHOFF, J
NORTH, RA
JOHNSON, SW
机构
[1] OREGON HLTH SCI UNIV,DEPT PHARMACOL,PORTLAND,OR 97201
[2] OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201
[3] VOLLUM INST ADV BIOMED RES,PORTLAND,OR 97201
关键词
SUBSTANTIA NIGRA; VENTRAL TEGMENTAL AREA; NORADRENALINE; INTERNEURON; POTASSIUM CURRENT; PHENYLEPHRINE;
D O I
10.1111/j.1460-9568.1995.tb00692.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 mu M) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine D-2 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 mu M) 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 GABA(A) receptor-mediated postsynaptic potentials recorded in both principal and secondary cells. We conclude that stimulation of alpha(1)-adrenergic receptors depolarizes principal (dopamine) neurons by reducing membrane conductance for potassium, but this effect is modulated by the increase in frequency of spontaneous inhibitory postsynaptic potentials evoked by stimulation of alpha(1)-adrenergic receptors located on local interneurons.
引用
收藏
页码:1707 / 1713
页数:7
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