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See detailMechanism of the medium-duration afterhyperpolarization in rat serotonergic neurons
Alix, Philippe ULg; Venkatesan, Kumar; Scuvée-Moreau, Jacqueline et al

in European Journal of Neuroscience (2014), 39(2), 186-196

Most serotonergic neurons display a prominent medium-duration afterhyperpolarization (mAHP), which is mediated by small conductance Ca2+-activated K+ (SK) channels. Recent ex vivo and in vivo experiments ... [more ▼]

Most serotonergic neurons display a prominent medium-duration afterhyperpolarization (mAHP), which is mediated by small conductance Ca2+-activated K+ (SK) channels. Recent ex vivo and in vivo experiments have suggested that SK channel blockade increases the firing rate and/or bursting in these neurons. The purpose of this study was therefore to characterize the source of Ca2+ which activates the mAHP channels in serotonergic neurons. In voltage clamp experiments, an outward current was recorded at -60 mV after a depolarizing pulse to + 100 mV. A supra-maximal concentration of the SK channel blockers apamin or (-)- bicuculline methiodide blocked this outward current. This current was also sensitive to the broad Ca2+ channel blocker Co2+ and was partially blocked by both ω-conotoxin and mibefradil, which are blockers of N-type and T-type Ca2+ channels, respectively. Neither blockers of other voltage-gated Ca2+ channels nor DBHQ, an inhibitor of Ca2+-induced Ca2+ release, had any effect on the SK current. [less ▲]

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See detailSK Channel blockade promotes burst firing in dorsal raphe serotonergic neurons
Rouchet, Nathalie; Waroux, Olivier ULg; Lamy, Cédric et al

in European Journal of Neuroscience (2008), 28(6), 1108-15

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See detailSK Channel blockade promotes burst firing in dorsal raphe serotonergic neurons
Rouchet, Nathalie ULg; Waroux, Olivier ULg; Lamy, Cédric ULg et al

in European Journal of Neuroscience (2008), 28(6), 1108-15

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See detailSK channels control the firing pattern of midbrain dopaminergic neurons in vivo
Waroux, Olivier ULg; Massotte, Laurent ULg; Alleva, Livia ULg et al

in European Journal of Neuroscience (2005), 22(12), 3111-3121

A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K ... [more ▼]

A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K+ channels of the SK type. However, due to the lack of suitable tools, in vivo evidence is lacking. We have taken advantage of the development of the water-soluble, medium potency SK blocker N-methyl-laudanosine (CH3-L) to test this hypothesis in anaesthetized rats. In the lateral ventral tegmental area, CH3-L iontophoresis onto dopaminergic neurons significantly increased the coefficient of variation of their interspike intervals and the percentage of spikes generated in bursts as compared to the control condition. The effect of CH3-L persisted in the presence of a specific GABA(A) antagonist, suggesting a direct effect. It was robust and reversible, and was also observed in the substantia nigra. Control experiments demonstrated that the effect of CH3-L could be entirely ascribed to its blockade of SK channels. On the other hand, the firing pattern of noradrenergic neurons was much less affected by CH3-L. We provide here the first demonstration of a major role of SK channels in the control of the switch between tonic and burst firing of dopaminergic neurons in physiological conditions. This study also suggests a new strategy to develop modulators of the dopaminergic (DA) system, which could be of interest in the treatment of Parkinson's disease, and perhaps other diseases in which DA pathways are dysfunctional. [less ▲]

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See detailDopamine activates noradrenergic receptors in the preoptic area
Cornil, Charlotte ULg; Balthazart, Jacques ULg; Motte, Patrick ULg et al

in Journal of Neuroscience (2002), 22(21), 9320-9330

Dopamine (DA) facilitates male sexual behavior and modulates aromatase activity in the quail preoptic area (POA). Aromatase neurons in the POA receive dopaminergic inputs, but the anatomical substrate ... [more ▼]

Dopamine (DA) facilitates male sexual behavior and modulates aromatase activity in the quail preoptic area (POA). Aromatase neurons in the POA receive dopaminergic inputs, but the anatomical substrate that mediates the behavioral and endocrine effects of DA is poorly understood. Intracellular recordings showed that 100 muM DA hyperpolarizes most neurons in the medial preoptic nucleus (80%) by a direct effect, but depolarizes a few others (10%). DA-induced hyperpolarizations were not blocked by D1 or D2 antagonists (SCH-23390 and sulpiride). Extracellular recordings confirmed that DA inhibits the firing of most cells (52%) but excites a few others (24%). These effects also were not affected by DA antagonists (SCH-23390 and sulpiride) but were blocked by alpha(2)-(yohimbine) and alpha(1)-(prazosin) noradrenergic receptor antagonists, respectively. Two dopamine-beta-hydroxylase (DBH) inhibitors (cysteine and fusaric acid) did not block the DA-induced effects, indicating that DA is not converted into norepinephrine (NE) to produce its effects. The pK(B) of yohimbine for the receptor involved in the DA- and NE-induced inhibitions was similar, indicating that the two monoamines interact with the same receptor. Together, these results demonstrate that the effects of DA in the POA are mediated mostly by the activation of alpha(2) (inhibition) and alpha(1) (excitation) adrenoreceptors. This may explain why DA affects the expression of male sexual behavior through its action in the POA, which contains high densities of alpha(2)-noradrenergic but limited amounts of DA receptors. This study thus clearly demonstrates the existence of a cross talk within CNS catecholaminergic systems between a neurotransmitter and heterologous receptors. [less ▲]

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See detailMethyl-laudanosine: A new pharmacological tool to investigate the function of small-conductance Ca2+-activated K+ channels
Scuvée-Moreau, Jacqueline ULg; Liégeois, Jean-François ULg; Massotte, Laurent ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2002), 302(3), 1176-1183

Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the prolonged postspike afterhyperpolarization (AHP) observed in many central neurons and play an important role in modulating ... [more ▼]

Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the prolonged postspike afterhyperpolarization (AHP) observed in many central neurons and play an important role in modulating neuronal activity. However, a lack of specific and reversible blockers of these channels hampers their study in various experimental conditions. Because previous work has shown that bicuculline salts block these channels, we examined whether related alkaloids, namely laudanosine quaternary derivatives, would produce similar effects. Intracellular recordings were performed on rat midbrain dopaminergic neurons and hippocampus CA1 pyramidal cells. Binding experiments were performed on rat cerebral cortex membranes. Laudanosine, methyl-laudanosine, and ethyl-laudanosine blocked the apamin-sensitive AHP of dopaminergic neurons with mean IC(50) values of 152, 15, and 47 microM, respectively. The benzyl and butyl derivatives were less potent. Methyl-laudanosine had no effect on the I(h) current, action potential parameters, or membrane resistance of dopaminergic cells, or on the decrease in input resistance induced by muscimol, indicating a lack of antagonism at GABA(A) receptors. Interestingly, 100 microM methyl-laudanosine induced a significant increase in spiking frequency of dopaminergic neurons but not of CA1 pyramidal cells, suggesting the possibility of regional selectivity. Binding experiments on laudanosine derivatives were in good agreement with electrophysiological data. Moreover, methyl-laudanosine has no affinity for voltage-gated potassium channels, and its affinity for SK channels (IC(50) 4 microM) is superior to its affinity for muscarinic (IC(50) 114 microM) and neuronal nicotinic (IC(50) > or =367 microM) receptors. Methyl-laudanosine may be a valuable pharmacological tool to investigate the role of SK channels in various experimental models. [less ▲]

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See detailEvidence for a Modulatory Role of Ih on the Firing of a Subgroup of Midbrain Dopamine Neurons
Seutin, Vincent ULg; Massotte, Laurent ULg; Renette, M. F. et al

in Neuroreport (2001), 12(2), 255-8

A previous investigation has suggested that the hyperpolarization-activated cation current Ih does not contribute to the spontaneous firing of midbrain dopaminergic neurons. This conclusion was reached ... [more ▼]

A previous investigation has suggested that the hyperpolarization-activated cation current Ih does not contribute to the spontaneous firing of midbrain dopaminergic neurons. This conclusion was reached using Cs(-1). We have re-examined this question with extracellular recordings in slices using the more specific blocker ZD7288. In two-thirds of the cells, low concentrations of ZD7288 induced a decrease of the spontaneous firing. The maximal inhibition was about 40% and the mean IC50 was 1.6 microM. This effect was probably direct because it persisted in the presence of antagonists of various receptors. These concentrations of ZD7288 had no effect in the remaining one third of the examined cells. However, the highest concentration of ZD7288 (300 microM) abolished the firing of all dopaminergic neurons, probably by a mechanism unrelated to the blockade of Ih. We conclude that Ih controls to a certain extent the firing of a majority of midbrain dopaminergic neurons. [less ▲]

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See detailCalcium Release from Internal Stores Is Required for the Generation of Spontaneous Hyperpolarizations in Dopaminergic Neurons of Neonatal Rats
Seutin, Vincent ULg; Mkahli, F.; Massotte, Laurent ULg et al

in Journal of Neurophysiology (2000), 83(1), 192-7

We recently have demonstrated the existence of spontaneous hyperpolarizations in midbrain dopaminergic neurons of neonatal but not adult rats. These events are mediated by the opening of apamin-sensitive ... [more ▼]

We recently have demonstrated the existence of spontaneous hyperpolarizations in midbrain dopaminergic neurons of neonatal but not adult rats. These events are mediated by the opening of apamin-sensitive K(+) channels after a rise in the intracellular concentration of Ca(2+). They are resistant to tetrodotoxin in most cases and are probably endogenous (i.e., not synaptically activated). Here their mechanism was investigated. Cyclopiazonic acid (10 microM), a specific inhibitor of endoplasmic reticulum Ca(2+) ATPases, reversibly abolished the events. Caffeine, which promotes Ca(2+) release from intracellular stores, had concentration-dependent effects. At 1 mM, it markedly and steadily increased the frequency and the amplitude of the hyperpolarizations. At 10 mM, it induced a transient increase in their frequency followed by their cessation. All these effects were quickly reversible. Ryanodine (10 microM), which decreases the conductance of Ca(2+) release channels, irreversibly blocked the spontaneous hyperpolarizations. Dantrolene (100 microM), a blocker of Ca(2+) release from sarcoplasmic reticulum of striated muscle, did not affect the events. On the other hand, Cd(2+) (100-300 microM), a broad antagonist of membrane voltage-gated Ca(2+) channels, significantly reduced the amplitude and the frequency of the hyperpolarizations. However, when the frequency of the events was increased by 1 mM caffeine, Cd(2+) affected them to a smaller extent, whereas cyclopiazonic acid still abolished them. We conclude that internal stores are the major source of Ca(2+) ions that induce the K(+) channel openings underlying the spontaneous hyperpolarizations of these neurons. [less ▲]

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See detailSpontaneous Apamin-Sensitive Hyperpolarizations in Dopaminergic Neurons of Neonatal Rats
Seutin, Vincent ULg; Massotte, Laurent ULg; Scuvée-Moreau, Jacqueline ULg et al

in Journal of Neurophysiology (1998), 80(6), 3361-4

Spontaneous apamin-sensitive hyperpolarizations in dopaminergic neurons of neonatal rats. J. Neurophysiol. 80: 3361-3364, 1998. Intracellular recordings from substantia nigra slices revealed the existence ... [more ▼]

Spontaneous apamin-sensitive hyperpolarizations in dopaminergic neurons of neonatal rats. J. Neurophysiol. 80: 3361-3364, 1998. Intracellular recordings from substantia nigra slices revealed the existence of spontaneous hyperpolarizations (amplitude 2-8 mV, duration 100-400 ms) at -60 mV in most dopaminergic neurons of neonatal (9-15 days) but not adult rats. These events were blocked by apamin (300 nM) and bicuculline methochloride (100-300 microM), which blocks apamin-sensitive currents. They were unaffected by the selective gamma-aminobutyric acid-A (GABAA) antagonists SR95531 (100 microM) and picrotoxin (30-50 microM), the GABAB antagonist CGP35348 (300 microM), the D2 antagonist haloperidol (1 microM), and the metabotropic antagonist MCPG (1 mM). The hyperpolarizations were strongly attenuated or abolished when recording electrodes contained 200 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. They were resistant to tetrodotoxin in the majority of the cells. They had some voltage dependency and were in some cases transiently potentiated when cells were briefly depolarized by current injection. We conclude that dopaminergic neurons have developmentally regulated physiological properties. These spontaneous hyperpolarizations might affect the firing rate of these cells, which was found to be lower in neonates than in adults. [less ▲]

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See detailEffect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro.
Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg; Vrijens, Bernard ULg et al

in Archives of Physiology & Biochemistry (1997), 105(5), 421-8

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices ... [more ▼]

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices. Pinacidil, lemakalim, diazoxide and a new compound, BPDZ44, had an inhibitory effect on the electrical activity of CA1 pyramidal cells. They all had a similar potency. Only BPDZ44 and diazoxide inhibited the firing rate of A10 dopamine neurons. The sulfonylurea glipizide (1 microM) antagonized the effect of BPDZ44 and diazoxide on A10 neurons but failed to antagonize the effect of KCOs on CA1 pyramidal cells. These results show that differences exist among KCOs in their ability to decrease the electrical activity of various populations of central neurons. [less ▲]

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See detailHydrogen Peroxide Hyperpolarizes Rat Ca1 Pyramidal Neurons by Inducing an Increase in Potassium Conductance
Seutin, Vincent ULg; Scuvée-Moreau, Jacqueline ULg; Massotte, Laurent ULg et al

in Brain Research (1995), 683(2), 275-8

It has been suggested that hydrogen peroxide is involved in cascades of pathological events affecting neural cells. The aim of this study was therefore to examine whether this molecule is able by itself ... [more ▼]

It has been suggested that hydrogen peroxide is involved in cascades of pathological events affecting neural cells. The aim of this study was therefore to examine whether this molecule is able by itself to modify membrane properties of pyramidal neurons in the CA1 region of the rat hippocampus. Intracellular recordings in the slice preparation showed that 3.3 mM hydrogen peroxide hyperpolarized all neurons tested (n = 41) by 11 +/- 3 mV. This effect persisted in the presence of tetrodotoxin. It developed slowly, was reversible and reproducible. In the presence of tetrodotoxin, the extrapolated reversal potential of this effect was -95 +/- 5 mV in 2.5 mM external potassium. This value was not significantly different from the one obtained with the GABAB agonist baclofen (10 microM) (-98 +/- 5 mV). It shifted when the concentration of external potassium was increased to 10.5 mM (from -96 +/- 5 to -62 +/- 4 mV), in close agreement with the Nernst equation potassium ions. The hyperpolarization was significantly reduced (by 65 +/- 22%) by the potassium channel blocker barium (100 microM). We suggest that hydrogen peroxide is able to induce an increase in potassium conductance in rat CA1 pyramidal neurons. The exact mechanism by which it produces this effect (direct action on channels or indirect effect) remains to be determined. [less ▲]

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See detailDifferential effects of picrotoxin and RO 15-1788 on high and low ethanol concentrations on rat locus coeruleus in vitro.
Verbanck, P. M.; Seutin, Vincent ULg; Massotte, Laurent ULg et al

in European Journal of Pharmacology (1992), 211(1), 15-21

In an in vitro electrophysiological single-cell recording model, ethanol had an inhibitory effect on locus coeruleus (LC) neurons at both low (0.1 mmol/l) and high (500 mmol/l) concentrations. In order to ... [more ▼]

In an in vitro electrophysiological single-cell recording model, ethanol had an inhibitory effect on locus coeruleus (LC) neurons at both low (0.1 mmol/l) and high (500 mmol/l) concentrations. In order to test if the benzodiazepine-GABA (gamma-aminobutyric acid) receptor complex could be implicated in this effect, we tested the interaction of these ethanol concentrations with picrotoxin (100 mmol/l) and RO 15-1788 (10 nmol/l). RO 15-1788 reversed the inhibitory effect induced by ethanol 500 mmol/l, but not by ethanol 0.1 mmol/l; picrotoxin reversed the effects of both concentrations. This indicates that the mechanisms of action of ethanol on LC neurons are not the same for high and low concentrations. Furthermore, the effect of concentrations related to a behavioral effect (greater than 10 mmol/l) was reversed by a low-calcium medium that abolishes transmitter release. Therefore, the inhibition induced by ethanol 500 mmol/l seems to be due to the release of an endogenous benzodiazepine-like compound. [less ▲]

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See detailAcute Amphetamine-Induced Subsensitivity of A10 Dopamine Autoreceptors in Vitro
Seutin, Vincent ULg; Verbanck, Paul; Massotte, Laurent ULg et al

in Brain Research (1991), 558(1), 141-4

Extracellular recordings were obtained from spontaneously active, presumed dopamine (DA) neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied (+)-amphetamine (AMPH ... [more ▼]

Extracellular recordings were obtained from spontaneously active, presumed dopamine (DA) neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied (+)-amphetamine (AMPH) (1-30 microM) induced a concentration-dependent decrease in the firing rate of these neurons, which tended to saturate with the highest concentrations used (n = 11). This inhibitory effect was dependent on the activation of D2 receptors since it was reversed by the D2 antagonist sulpiride (n = 8). However, the most striking effect of AMPH was the induction of a prominent subsensitivity of DA autoreceptors: whereas in 18 out of 20 control neurons, the D2 agonist BHT 920 (100 nM) produced a rapid and complete inhibition of the firing, this was observed in none out of 11 neurons 10 min after the end of the application of AMPH (1-30 microM) (P less than 0.001). In these cells, the mean percent inhibition produced by BHT 920 was only 47 +/- 8%. This subsensitivity remained unchanged after 20 min and declined after one hour. This effect was specific, since the sensitivity of GABAB receptors to baclofen (500 nM-1 microM) was not modified by the application of AMPH (n = 12). These results suggest that AMPH-induced DA autoreceptor subsensitivity can be produced acutely and may be the first step in a cascade of events leading to behavioral sensitization to this compound. [less ▲]

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See detailYohimbine can induce ethanol tolerance in an in vitro preparation of rat locus coeruleus.
Verbanck, P.; Seutin, Vincent ULg; Massotte, Laurent ULg et al

in Alcoholism, Clinical & Experimental Research (1991), 15(6), 1036-9

Noradrenergic neurons have been implicated in the development of ethanol dependence and tolerance. Moreover, the development of an hyposensitivity of alpha 2 adrenoceptors has been postulated during long ... [more ▼]

Noradrenergic neurons have been implicated in the development of ethanol dependence and tolerance. Moreover, the development of an hyposensitivity of alpha 2 adrenoceptors has been postulated during long-term exposition to ethanol. In order to test the putative role of alpha 2 receptors in ethanol intoxication, we have studied the interaction between ethanol and yohimbine, an alpha 2 antagonist, on the spontaneous firing rate of rat locus coeruleus (LC) in an in vitro slice model. The spikes from single neurons were recorded by glass microelectrodes. Ethanol at 100 mM, a concentration that parallels the behavioral effects in the human and in the animals, inhibits the firing activity of some LC cells. This inhibition was quickly reversed after stopping the ethanol perfusion and was observed for each further administration. However, if yohimbine (20 microM) was simultaneously perfused, the ethanol-induced inhibition was rapidly antagonized. This effect is reversible after long time washout of yohimbine. This suggests that alpha 2 adrenoceptors could be implicated in the inhibitory effect of ethanol on LC noradrenergic neurons and perhaps in the development of tolerance. However, other hypotheses are discussed, because yohimbine can also antagonize other types of receptors. [less ▲]

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See detailEvidence for the presence of N-methyl-D-aspartate receptors in the ventral tegmental area of the rat : an electrophysiological in vitro study
Seutin, Vincent ULg; Verbanck, Paul; Massotte, Laurent ULg et al

in Brain Research (1990), 514(1), 147-150

Extracellular recordings were obtained from spontaneously active, presumed dopaminergic neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied N-methyl-D-aspartate ... [more ▼]

Extracellular recordings were obtained from spontaneously active, presumed dopaminergic neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied N-methyl-D-aspartate (NMDA) (1-20 microM) activated all neurons tested (n = 36). This effect was clearly concentration-dependent (n = 14), quickly reversible and reproducible. No bursting type of discharge was observed during NMDA infusion. The NMDA receptor blocker DL-2-amino-5-phosphonovaleric acid (50 microM) reversibly antagonized the increase in cell firing produced with 10 microM NMDA by 83.5 +/- 3% (mean +/- S.E.M.) (n = 8, P less than 0.05). Lowering the Mg2+ concentration of the perfusion fluid to one-third of its normal value significantly enhanced the excitatory effect of 5 microM NMDA (n = 7, P less than 0.05), but not of 500 nM carbachol (n = 6). Finally, NMDA did not modify the sensitivity of dopaminergic autoreceptors of VTA neurons (n = 8), when compared to controls (n = 10). These observations strongly support the presence of specific NMDA receptors in the VTA. [less ▲]

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See detailElectrophysiological effects of ethanol on monoaminergic neurons: an in vivo and in vitro study.
Verbanck, P.; Seutin, Vincent ULg; Dresse, Albert ULg et al

in Alcoholism, Clinical & Experimental Research (1990), 14(5), 728-35

Monoaminergic neurons have been shown to play a role in both the intoxicating and chronic effects of ethanol. We present here the results of a study about the acute effects of ethanol on serotonergic ... [more ▼]

Monoaminergic neurons have been shown to play a role in both the intoxicating and chronic effects of ethanol. We present here the results of a study about the acute effects of ethanol on serotonergic raphe nucleus, noradrenergic locus coeruleus, and dopaminergic ventral tegmental area. These nuclei were investigated electrophysiologically by recording the spontaneous firing rate of single neurons using glass microelectrodes, both in vivo in chloral hydrate anesthetized rats and in vitro in brain slices. Ethanol was perfused intravenously at a rate ranging from 0.2 mg/kg/min to 0.2 g/kg/min in vivo, and at concentrations between 10(-8) M and 1 M in vitro. We observed that each monoaminergic nucleus had its own pattern of responses to acute ethanol perfusion, and that high and low concentrations have different actions, suggesting a biphasic effect. For example, in slices, ethanol concentrations higher than 10 mM induce an excitation in most raphe and ventral tegmental area neurons, and an inhibition of firing in locus coeruleus neurons. The results were comparable in the in vivo model, but much more heterogenous. We conclude that the effect of ethanol on the monoaminergic neurons is specific of the type of neuron, and that a biphasic effect is commonly found. [less ▲]

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See detailEffect of BHT-920 on monoaminergic neurons of the rat brain : an electrophysiological in vivo and in vitro study
Seutin, Vincent ULg; Scuvée-Moreau, Jacqueline ULg; Giesbers, Irène ULg et al

in Mededelingen van de Faculteit Landbouwwetenschappen (Rijksuniversiteit te Gent) (1990), 342

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See detailComparison of the Effect of Morphine on Locus Coeruleus Noradrenergic and Ventral Tegmental Area Dopaminergic Neurons in Vitro
Seutin, Vincent ULg; Franchimont, Nathalie; Massotte, Laurent ULg et al

in Life Sciences (1990), 46(25), 1879-85

Extracellular single-cell recordings were performed on rat brain slices to compare the effects of morphine on noradrenergic neurons of the locus coeruleus (LC) and on dopaminergic neurons of the ventral ... [more ▼]

Extracellular single-cell recordings were performed on rat brain slices to compare the effects of morphine on noradrenergic neurons of the locus coeruleus (LC) and on dopaminergic neurons of the ventral tegmental area (VTA). Morphine inhibited the firing of LC neurons at very low concentrations. The mean IC50 was 13.4 +/- 1nM (mean +/- SEM) (n = 7). Moreover, the inhibitory effect of morphine was identical in slices obtained from rats anesthetized with chloral hydrate or from non-anesthetized rats. On the contrary, morphine did not have any influence on the firing of most VTA neurons (N = 20) up to 100 microM, and did not modify the sensitivity of their autoreceptors (N = 8). It is concluded that morphine potently inhibits the firing of LC neurons in vitro both in slices of anesthetized and not anesthetized animals and has no direct excitatory effect on VTA dopaminergic neurons of the rat. [less ▲]

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