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Peter H Seeburg - One of the best experts on this subject based on the ideXlab platform.
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comparison of in vitro binding properties of a series of Dopamine Antagonists and agonists for cloned human Dopamine d2s and d2l receptors and for d2 receptors in rat striatal and mesolimbic tissues using 125i 2 iodospiperone
Psychopharmacology, 1993Co-Authors: Josee E Leysen, W Gommeren, J Mertens, Walter Luyten, P J Pauwels, Markus Ewert, Peter H SeeburgAbstract:We investigated the ligand binding properties in vitro of two splice variants of the cloned human Dopamine D2 receptor (the 443 and 414 amino acids long forms called D2L and D2S, respectively), expressed in 293 human kidney cells, in comparison with those of the Dopamine D2 receptors in rat striatum, nucleus accumbens and tuberculum olfactorium. The new radioligand, [125I]2′-iodospiperone, showed a similar high binding affinity (KD:0.056–0.122 nM) for cloned human D2S and D2L receptors and for the D2 receptors in the three rat brain areas. Binding affinities of 25 Dopamine Antagonists and of 10 Dopamine agonists belonging to different chemical classes were measured. The IC50 values of the Antagonists were virtually identical in the five preparations: spiperone was the most potent compound (pIC50 ≲ 9.9), remoxipride the least potent one (pIC50 ≲ 5.7). The agonists showed similar IC50 values for the cloned human D2S and D2L receptors but their affinity for rat brain D2 receptors was 2- to 5-fold higher. Dopamine showed shallow inhibition curves, the high affinity binding was 10-fold lower for the cloned human D2 receptors than for the rat brain D2 receptors. Addition of stable guanosine-5′-triphosphate (GTP) analogues shifted the D2 receptors in the rat brain tissues to the “low” affinity state, the low affinity binding of Dopamine was equal to the affinity for the cloned human receptor. None of the Dopamine Antagonists or agonists could differentiate between the two splice forms of the cloned human D2 receptors or between the D2 receptors in rat striatal and mesolimbic tissues. The lower apparent affinity of some agonists and of Dopamine in the absence of stable GTP analogues suggests a less appropriate receptor G-protein coupling for the cloned human D2 receptors expressed in the 293 human kidney cells. Unexpectedly, guanosine-5′-O-(3-thiotriphosphate) (GTP-γ-S) reduced the [125I]2′-iodospiperone binding to the D2 receptors by 20–35% in the rat brain tissues and the cloned human D2L receptor, and by 75% to the cloned human D2S receptor. The inhibition in the last case could be prevented partly by submicromolar concentrations of Dopamine. The GTP-γ-S effect is suggested to be due to reduction of disulphide bonds in the receptor. Recent molecular modelling studies indicated an important role of the disulphide bridge between Cys107 at the start of transmembrane domain three and Cys182 in the third extracellular loop, for the binding of Dopamine to the D2 receptor.
Mark R Wightman - One of the best experts on this subject based on the ideXlab platform.
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Neuron Report Coordinated Accumbal Dopamine Release and Neural Activity Drive Goal-Directed Behavior
2013Co-Authors: Joseph F Cheer, Michael L Heien, Andrew T Seipel, Regina M Carelli, On J. Aragona, Mark R WightmanAbstract:Intracranial self-stimulation (ICSS) activates the neural pathways that mediate reward, including Dopaminergic terminal areas such as the nucleus accumbens (NAc). However, a direct role of Dopamine in ICSS-mediated reward has been questioned. Here, simultaneous voltammetric and electrophysiological recordings from the same electrode reveal that, at certain sites, the onset of anticipatory Dopamine surges and changes in neuronal firing patterns during ICSS are coincident, whereas sites lacking Dopamine changes also lack patterned firing. Intrashell microinfusion of a D1, but not a D2 receptor antagonist, blocks ICSS. An iontophoresis approach was implemented to explore the effect of Dopamine Antagonists on firing patterns without altering behavior. Similar to the microinfusion experiments, ICSS-related firing is selectively attenuated following D1 receptor blockade. This work establishes a temporal link between anticipatory rises of Dopamine and firing patterns in the NAc shell during ICSS and suggests that they may play a similar role with natural rewards and during drug self-administration
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coordinated accumbal Dopamine release and neural activity drive goal directed behavior
Neuron, 2007Co-Authors: Joseph F Cheer, Brandon J Aragona, Michael L Heien, Andrew T Seipel, Regina M Carelli, Mark R WightmanAbstract:Intracranial self-stimulation (ICSS) activates the neural pathways that mediate reward, including Dopaminergic terminal areas such as the nucleus accumbens (NAc). However, a direct role of Dopamine in ICSS-mediated reward has been questioned. Here, simultaneous voltammetric and electrophysiological recordings from the same electrode reveal that, at certain sites, the onset of anticipatory Dopamine surges and changes in neuronal firing patterns during ICSS are coincident, whereas sites lacking Dopamine changes also lack patterned firing. Intrashell microinfusion of a D1, but not a D2 receptor antagonist, blocks ICSS. An iontophoresis approach was implemented to explore the effect of Dopamine Antagonists on firing patterns without altering behavior. Similar to the microinfusion experiments, ICSS-related firing is selectively attenuated following D1 receptor blockade. This work establishes a temporal link between anticipatory rises of Dopamine and firing patterns in the NAc shell during ICSS and suggests that they may play a similar role with natural rewards and during drug self-administration.
Josee E Leysen - One of the best experts on this subject based on the ideXlab platform.
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comparison of in vitro binding properties of a series of Dopamine Antagonists and agonists for cloned human Dopamine d2s and d2l receptors and for d2 receptors in rat striatal and mesolimbic tissues using 125i 2 iodospiperone
Psychopharmacology, 1993Co-Authors: Josee E Leysen, W Gommeren, J Mertens, Walter Luyten, P J Pauwels, Markus Ewert, Peter H SeeburgAbstract:We investigated the ligand binding properties in vitro of two splice variants of the cloned human Dopamine D2 receptor (the 443 and 414 amino acids long forms called D2L and D2S, respectively), expressed in 293 human kidney cells, in comparison with those of the Dopamine D2 receptors in rat striatum, nucleus accumbens and tuberculum olfactorium. The new radioligand, [125I]2′-iodospiperone, showed a similar high binding affinity (KD:0.056–0.122 nM) for cloned human D2S and D2L receptors and for the D2 receptors in the three rat brain areas. Binding affinities of 25 Dopamine Antagonists and of 10 Dopamine agonists belonging to different chemical classes were measured. The IC50 values of the Antagonists were virtually identical in the five preparations: spiperone was the most potent compound (pIC50 ≲ 9.9), remoxipride the least potent one (pIC50 ≲ 5.7). The agonists showed similar IC50 values for the cloned human D2S and D2L receptors but their affinity for rat brain D2 receptors was 2- to 5-fold higher. Dopamine showed shallow inhibition curves, the high affinity binding was 10-fold lower for the cloned human D2 receptors than for the rat brain D2 receptors. Addition of stable guanosine-5′-triphosphate (GTP) analogues shifted the D2 receptors in the rat brain tissues to the “low” affinity state, the low affinity binding of Dopamine was equal to the affinity for the cloned human receptor. None of the Dopamine Antagonists or agonists could differentiate between the two splice forms of the cloned human D2 receptors or between the D2 receptors in rat striatal and mesolimbic tissues. The lower apparent affinity of some agonists and of Dopamine in the absence of stable GTP analogues suggests a less appropriate receptor G-protein coupling for the cloned human D2 receptors expressed in the 293 human kidney cells. Unexpectedly, guanosine-5′-O-(3-thiotriphosphate) (GTP-γ-S) reduced the [125I]2′-iodospiperone binding to the D2 receptors by 20–35% in the rat brain tissues and the cloned human D2L receptor, and by 75% to the cloned human D2S receptor. The inhibition in the last case could be prevented partly by submicromolar concentrations of Dopamine. The GTP-γ-S effect is suggested to be due to reduction of disulphide bonds in the receptor. Recent molecular modelling studies indicated an important role of the disulphide bridge between Cys107 at the start of transmembrane domain three and Cys182 in the third extracellular loop, for the binding of Dopamine to the D2 receptor.
Joseph F Cheer - One of the best experts on this subject based on the ideXlab platform.
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Neuron Report Coordinated Accumbal Dopamine Release and Neural Activity Drive Goal-Directed Behavior
2013Co-Authors: Joseph F Cheer, Michael L Heien, Andrew T Seipel, Regina M Carelli, On J. Aragona, Mark R WightmanAbstract:Intracranial self-stimulation (ICSS) activates the neural pathways that mediate reward, including Dopaminergic terminal areas such as the nucleus accumbens (NAc). However, a direct role of Dopamine in ICSS-mediated reward has been questioned. Here, simultaneous voltammetric and electrophysiological recordings from the same electrode reveal that, at certain sites, the onset of anticipatory Dopamine surges and changes in neuronal firing patterns during ICSS are coincident, whereas sites lacking Dopamine changes also lack patterned firing. Intrashell microinfusion of a D1, but not a D2 receptor antagonist, blocks ICSS. An iontophoresis approach was implemented to explore the effect of Dopamine Antagonists on firing patterns without altering behavior. Similar to the microinfusion experiments, ICSS-related firing is selectively attenuated following D1 receptor blockade. This work establishes a temporal link between anticipatory rises of Dopamine and firing patterns in the NAc shell during ICSS and suggests that they may play a similar role with natural rewards and during drug self-administration
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coordinated accumbal Dopamine release and neural activity drive goal directed behavior
Neuron, 2007Co-Authors: Joseph F Cheer, Brandon J Aragona, Michael L Heien, Andrew T Seipel, Regina M Carelli, Mark R WightmanAbstract:Intracranial self-stimulation (ICSS) activates the neural pathways that mediate reward, including Dopaminergic terminal areas such as the nucleus accumbens (NAc). However, a direct role of Dopamine in ICSS-mediated reward has been questioned. Here, simultaneous voltammetric and electrophysiological recordings from the same electrode reveal that, at certain sites, the onset of anticipatory Dopamine surges and changes in neuronal firing patterns during ICSS are coincident, whereas sites lacking Dopamine changes also lack patterned firing. Intrashell microinfusion of a D1, but not a D2 receptor antagonist, blocks ICSS. An iontophoresis approach was implemented to explore the effect of Dopamine Antagonists on firing patterns without altering behavior. Similar to the microinfusion experiments, ICSS-related firing is selectively attenuated following D1 receptor blockade. This work establishes a temporal link between anticipatory rises of Dopamine and firing patterns in the NAc shell during ICSS and suggests that they may play a similar role with natural rewards and during drug self-administration.
Andrea Mele - One of the best experts on this subject based on the ideXlab platform.
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Co-activation of glutamate and Dopamine receptors within the nucleus accumbens is required for spatial memory consolidation in mice.
Psychopharmacology, 2005Co-Authors: Valentina Ferretti, Cédrick Florian, Vivian J A Costantini, Pascal Roullet, Arianna Rinaldi, Elvira De Leonibus, Alberto Oliverio, Andrea MeleAbstract:RATIONALE: The nucleus accumbens receives glutamatergic and Dopaminergic inputs converging onto common dendrites. Recent behavioral data demonstrated that intra-accumbens administrations of either glutamate or Dopamine (DA) antagonist impair spatial memory consolidation. Thus, also based on the biochemical and molecular findings demonstrating interactions among the different receptors subtypes for glutamate and Dopamine, it is conceivable that memory consolidation within this structure might be modulated by glutamate-Dopamine receptor interactions. OBJECTIVES: The purpose of this study was to examine the effects of intra-accumbens co-administrations of glutamate and DA Antagonists on the consolidation of spatial information. METHODS: On day 1, CD1 male mice were placed in an open field containing five different objects and immediately after three sessions of habituation the animals were injected intra-accumbens with either vehicle or low doses of the N-methyl-D: -aspartate (NMDA; AP-5 50 ng/side), the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; DNQX 5 ng/side), the D1 (SCH23390 12.5 ng/side) and the D2 (sulpiride 25 ng/side) Antagonists that were ineffective alone in disrupting object displacement. Separate groups were then focally injected with a combination of one of the glutamate Antagonists with one of the Dopamine Antagonists. Twenty-four hours later, the ability of mice to discriminate object displacement was assessed. RESULTS: Controls and mice injected with ineffective doses of the NMDA, the AMPA, the D1 or the D2 Antagonists were always able to react to the object displacement. On the contrary, the groups administered with the different combinations (AP-5 and SCH23390, AP-5 and sulpiride, DNQX and SCH23390, DNQX and sulpiride) of glutamate and Dopamine Antagonists did not discriminate the spatial change. CONCLUSIONS: These results demonstrate that glutamate-Dopamine receptor interactions within the accumbens are essential for the consolidation process of spatial information.