Alpha₁‐adrenergic Effects on Dopamine Neurons Recorded Intracellularly in the Rat Midbrain Slice

Abstract

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)

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

“…Additionally, the α 1 -adrenergic receptor agonist phenylephrine depolarized VTA neurons in rat brain slices (Grenhoff et al 1995). In the present experiments prazosin microinjections into the VTA of rats prior to systemic administration of MDMA decreased the locomotor response to MDMA, suggesting that activation of α 1 -adrenoceptors in this region plays a role in the behavioral consequences of MDMA administration.…”

Previous Exposure to Cocaine Enhances Cocaine Self-Administration in an Alpha 1-Adrenergic Receptor Dependent Manner

“…Systemic or local administration of prazosin into the prefrontal cortex blocks increased DA and locomotor responses induced by systemic D-amphetamine (Darracq et al, 1998). Prazosin decreased spontaneous bursting of VTA DA cells (Grenhoff and Svensson, 1993), whereas direct application of an alpha 1-adrenergic receptor agonist, phenylephrine, in brain slices, depolarized some cells (Grenhoff et al, 1995). Increases burst firing of VTA DA cells was induced by systemic administration of reboxetin, a specific inhibitor of the NE transporter (Linner et al, 2001).…”

Noradrenaline transporter blockers raise extracellular dopamine in medial prefrontal but not parietal and occipital cortex: differences with mianserin and clozapine

“…Although clozapine has pronounced a 1 receptor blocking properties (Brunello et al 1995), a role of these properties in the increase of DA in cortical areas is unlikely, given the evidence that relatively selective blockade of a 1 receptors by prazosin does not increase dialysate DA in the PFCX (Gobert et al 1998). Indeed, stimulation of DA release in the cortex might eventually result from stimulation rather than blockade of a 1 receptors in the ventral tegmental area (VTA), through facilitation of burst firing of DA neurones (Grenhoff et al 1993(Grenhoff et al , 1995. However, Hertel et al (1999) and Linner et al (2001) failed to increase extracellular DA in the medial PFCX after intra-VTA infusion of a 2 antagonists or reboxetine.…”