Noradrenaline increases the firing rate of a subpopulation of rat subthalamic neurones through the activation of α1-adrenoceptors

Arcos, Demetrio; Sierra, Arturo; Nuñez, Alejandro; Flores, Gonzalo; Aceves, Jorge; Arias‐Montaño, José‐Antonio

doi:10.1016/s0028-3908(03)00315-0

Cited by 30 publications

(24 citation statements)

References 44 publications

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“…In fact, tyramine has been shown to potently release noradrenaline and inhibit its uptake (Rothman et al, 2001). Moreover, noradrenaline has been shown to excite STN neurons by stimulation of adrenergic α 1 receptors (Arcos et al, 2003). In confirming this finding, we found that noradrenaline (30 μM) evoked 12.9 ± 1.7 pA of inward current in STN neurons (n = 7).…”

Section: Tyramine-induced Inward Current Is Dopamine-dependentsupporting

confidence: 79%

Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism

2007

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Tyramine, an endogenous ligand for mammalian trace amine-associated receptors, may act as a neuromodulator that regulates neuronal activity in basal ganglia. Using whole-cell patch recordings of subthalamic nucleus (STN) neurons in rat brain slices, we found that bath application of tyramine evoked an inward current in voltage-clamp in over 60% of all STN neurons. The inward current induced by tyramine was mimicked by the D 2 -like dopamine receptor agonist quinpirole, but was only partially blocked by the D 2 -like receptor antagonist sulpiride. In contrast, the D 1 -like receptor agonist SKF38393 evoked no current in STN neurons. Inward current evoked by tyramine was significantly reduced by the catecholamine uptake inhibitor nomifensine, and by exhausting catecholamines in the brain via pre-treatment with reserpine. Tyramine also reduced the amplitude of GABA A receptor-mediated IPSCs that were evoked by focal electrical stimulation of the slice. Inhibition of IPSCs by tyramine was mimicked by quinpirole and was blocked by sulpiride but not by SCH23390, a D 1 receptor antagonist. Moreover, tyramine-induced inhibition of IPSCs was reduced in slices pre-treated with reserpine, and this inhibition could be restored by briefly superfusing the slice with dopamine. These results suggest that tyramine acts as an indirect dopamine agonist in the STN. Although inhibition of IPSCs are mediated by D 2 -like receptors, the dopaminedependent inward currents evoked by tyramine do not fit a typical dopamine receptor pharmacological profile.

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Section: Tyramine-induced Inward Current Is Dopamine-dependentsupporting

confidence: 79%

Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism

2007

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“…Although primarily under the control of pallidal and cortical afferents, STN is also modulated by DA (Ni et al, 2001b;Baufreton et al, 2003;Cragg et al, 2004) and 5-HT (Stanford et al, 2005;Xiang et al, 2005). However, NE modulation of STN is not documented (but see Arcos et al, 2003), although noradrenergic fibers arising from LC have been shown in the STN (Canteras et al, 1990;Parent and Hazrati, 1995). Whereas the "excitatory" ␣1-AR are thought to be located on postsynaptic membrane and the "inhibitory" ␣2-AR on presynaptic nerve terminals (Langer, 1974;Starke et al, 1974;Lakhlani et al, 1996), their actual distribution in the STN was not documented.…”

Section: Ne Innervation Of Stnmentioning

confidence: 99%

“…Because very little information is available on noradrenergic control of STN neuronal activity (Arcos et al, 2003), we investigated the effects of ␣1-AR and ␣2-AR agonists and antagonists during locomotor activity of intact and 6-OHDAlesioned rats and extracellular single unit activity of STN neurons in both experimental conditions after systemic administration of drugs. Assumptions about the direct effects of these agents were also examined in rat brain slices using patch-clamp recording technique, and actual anatomical localization of ␣1-AR and ␣2-AR was confirmed using immunohistochemistry.…”

Section: Introductionmentioning

confidence: 99%

Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats

Belujon¹,

Bézard²,

Taupignon³

et al. 2007

J. Neurosci.

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The subthalamic nucleus (STN) plays a key role in the pathophysiology of Parkinson's disease. The modulation of the STN by norepinephrine, however, is unknown. The present study aims at characterizing the effects of systemic administration of noradrenergic agents on locomotor activity and on in vivo extracellularly recorded STN neuronal activity in intact and 6-hydroxydopamine (6-OHDA)-lesioned rats. Using selective agonists and antagonists of ␣1 and ␣2 adrenergic receptors (ARs), we show that STN neurons have functional ␣1-and ␣2-AR controlling STN firing with an impact on locomotor activity. We further demonstrate that those systemic effects are supported, at least in part, by a direct modulation of STN neuronal activity, using patch-clamp recordings of STN neurons in brain slices. These findings support the premise that hypokinesia is associated with an increased STN neuronal activity, and that improvements of parkinsonian motor abnormalities are associated with a decrease in STN activity. Our data challenge assumptions about the role of ␣1-AR and ␣2-AR in the regulation of STN neurons in both intact and 6-OHDA-lesioned rats and further ground the rationale for using ␣2-AR noradrenergic antagonists in Parkinson's disease, albeit via an unexpected mechanism.

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“…These conditions result in a mostly tonic and uncorrelated (among neurons) pattern of activity which is almost independent of GABAergic and glutamatergic signalling such as remains in these slices (Fujimoto and Kita 1993;Bevan and Wilson 1999;Wilson et al 2004;Xiang et al 2005). However, it is sensitive to external application of 5-HT and norepinephrine (Arcos et al 2003;Xiang et al 2005;Stanford et al 2005;Shen et al 2007). Thus, standard brain slices of STN appear suitable for the detection of action potential-independent release of these transmitters by MDMA, and an investigation of the role of diverse neurotransmitter receptor subtypes in the alteration of the basal (tonic) firing rate of STN neurons by MDMA.…”

Section: Stn Neurons In Vitro: Homogeneous Firing Patterns Heterogenmentioning

confidence: 96%

“…2d). However, we had no means to decide whether excited versus inhibited neurons represented pharmacologically distinct subpopulations, as has been surmised (Arcos et al 2003;Stanford et al 2005), or simply reflected a continuum, and therefore did not subdivide them.…”

Section: Stn Neurons In Vitro: Homogeneous Firing Patterns Heterogenmentioning

confidence: 99%

MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro

2014

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3,4-Methylene-dioxy-N-methylamphetamine (MDMA, 'ecstasy') has a broad spectrum of molecular targets in the brain, among them receptors and transporters of the serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic systems. Its action on the serotonergic system modulates motor systems in rodents and humans. Although parts of the basal ganglia could be identified as mediators of the motor effects of MDMA, very little is known about the role of the subthalamic nucleus (STN). Therefore, this study investigated the modulation of spontaneous action potential activity of the STN by MDMA (2.5-20 µM) in vitro. MDMA had very heterogeneous effects, ranging from a complete but reversible inhibition to a more than twofold increase in firing at 5 µM. On average, MDMA excited STN neurons moderately, but lost its excitatory effect in the presence of the 5-HT(2A) antagonist MDL 11,939. 5-HT(1A) receptors did not appear to play a major role. Effects of MDMA on transporters for serotonin (SERT) and norepinephrine (NET) were investigated by coapplication of the reuptake inhibitors citalopram and desipramine, respectively. Similar to the effects of 5-HT(2A) receptor blockade, antagonism of SERT and NET bestowed an inhibitory effect on MDMA. From these results, we conclude that both the 5-HT and the noradrenergic system mediate MDMA-induced effects on STN neurons.

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Noradrenaline increases the firing rate of a subpopulation of rat subthalamic neurones through the activation of α1-adrenoceptors

Cited by 30 publications

References 44 publications

Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism

Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism

Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats

MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro

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