GABA Agonist

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Esa R Korpi - One of the best experts on this subject based on the ideXlab platform.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABAA receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABAA receptor α6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1α6) mice ectopically expressing α6 subunits especially in the hippocampus to study how extrasynaptically enriched αβ(γ2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic α6β receptors make up about 10% of the hippocampal GABAA receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1α6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1α6 mice, the α6β receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [35S]TBPS binding to the GABAA receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABAA receptors revealed that GABA was a partial Agonist at α6β3 and α6β3δ receptors, but a full Agonist at α6β3γ2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic αβ GABAA receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABA(A) receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABA(A) receptor alpha6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1alpha6) mice ectopically expressing alpha6 subunits especially in the hippocampus to study how extrasynaptically enriched alphabeta(gamma2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic alpha6beta receptors make up about 10% of the hippocampal GABA(A) receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1alpha6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1alpha6 mice, the alpha6beta receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [(35)S]TBPS binding to the GABA(A) receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABA(A) receptors revealed that GABA was a partial Agonist at alpha6beta3 and alpha6beta3delta receptors, but a full Agonist at alpha6beta3gamma2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic alphabeta GABA(A) receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

Kati S Saarelainen - One of the best experts on this subject based on the ideXlab platform.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABAA receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABAA receptor α6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1α6) mice ectopically expressing α6 subunits especially in the hippocampus to study how extrasynaptically enriched αβ(γ2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic α6β receptors make up about 10% of the hippocampal GABAA receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1α6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1α6 mice, the α6β receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [35S]TBPS binding to the GABAA receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABAA receptors revealed that GABA was a partial Agonist at α6β3 and α6β3δ receptors, but a full Agonist at α6β3γ2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic αβ GABAA receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABA(A) receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABA(A) receptor alpha6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1alpha6) mice ectopically expressing alpha6 subunits especially in the hippocampus to study how extrasynaptically enriched alphabeta(gamma2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic alpha6beta receptors make up about 10% of the hippocampal GABA(A) receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1alpha6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1alpha6 mice, the alpha6beta receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [(35)S]TBPS binding to the GABA(A) receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABA(A) receptors revealed that GABA was a partial Agonist at alpha6beta3 and alpha6beta3delta receptors, but a full Agonist at alpha6beta3gamma2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic alphabeta GABA(A) receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

Martin Ranna - One of the best experts on this subject based on the ideXlab platform.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABAA receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABAA receptor α6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1α6) mice ectopically expressing α6 subunits especially in the hippocampus to study how extrasynaptically enriched αβ(γ2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic α6β receptors make up about 10% of the hippocampal GABAA receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1α6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1α6 mice, the α6β receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [35S]TBPS binding to the GABAA receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABAA receptors revealed that GABA was a partial Agonist at α6β3 and α6β3δ receptors, but a full Agonist at α6β3γ2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic αβ GABAA receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABA(A) receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABA(A) receptor alpha6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1alpha6) mice ectopically expressing alpha6 subunits especially in the hippocampus to study how extrasynaptically enriched alphabeta(gamma2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic alpha6beta receptors make up about 10% of the hippocampal GABA(A) receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1alpha6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1alpha6 mice, the alpha6beta receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [(35)S]TBPS binding to the GABA(A) receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABA(A) receptors revealed that GABA was a partial Agonist at alpha6beta3 and alpha6beta3delta receptors, but a full Agonist at alpha6beta3gamma2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic alphabeta GABA(A) receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

Holger Rabe - One of the best experts on this subject based on the ideXlab platform.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABAA receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABAA receptor α6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1α6) mice ectopically expressing α6 subunits especially in the hippocampus to study how extrasynaptically enriched αβ(γ2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic α6β receptors make up about 10% of the hippocampal GABAA receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1α6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1α6 mice, the α6β receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [35S]TBPS binding to the GABAA receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABAA receptors revealed that GABA was a partial Agonist at α6β3 and α6β3δ receptors, but a full Agonist at α6β3γ2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic αβ GABAA receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABA(A) receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABA(A) receptor alpha6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1alpha6) mice ectopically expressing alpha6 subunits especially in the hippocampus to study how extrasynaptically enriched alphabeta(gamma2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic alpha6beta receptors make up about 10% of the hippocampal GABA(A) receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1alpha6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1alpha6 mice, the alpha6beta receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [(35)S]TBPS binding to the GABA(A) receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABA(A) receptors revealed that GABA was a partial Agonist at alpha6beta3 and alpha6beta3delta receptors, but a full Agonist at alpha6beta3gamma2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic alphabeta GABA(A) receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

Saku T Sinkkonen - One of the best experts on this subject based on the ideXlab platform.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABAA receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABAA receptor α6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1α6) mice ectopically expressing α6 subunits especially in the hippocampus to study how extrasynaptically enriched αβ(γ2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic α6β receptors make up about 10% of the hippocampal GABAA receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1α6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1α6 mice, the α6β receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [35S]TBPS binding to the GABAA receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABAA receptors revealed that GABA was a partial Agonist at α6β3 and α6β3δ receptors, but a full Agonist at α6β3γ2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic αβ GABAA receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.

  • enhanced behavioral sensitivity to the competitive GABA Agonist gaboxadol in transgenic mice over expressing hippocampal extrasynaptic α6β GABAa receptors
    Journal of Neurochemistry, 2008
    Co-Authors: Kati S Saarelainen, Martin Ranna, Holger Rabe, Saku T Sinkkonen, Tommi Moykkynen, Mikko Uusioukari, Hartmut Luddens, Annimaija Linden, Esa R Korpi
    Abstract:

    The behavioral and functional significance of the extrasynaptic inhibitory GABA(A) receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABA(A) receptor alpha6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1alpha6) mice ectopically expressing alpha6 subunits especially in the hippocampus to study how extrasynaptically enriched alphabeta(gamma2)-type receptors alter animal behavior and receptor responses. In these mice extrasynaptic alpha6beta receptors make up about 10% of the hippocampal GABA(A) receptors resulting in imbalance between synaptic and extrasynaptic inhibition. The synthetic GABA-site competitive Agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; 3 mg/kg) induced remarkable anxiolytic-like response in the light : dark exploration and elevated plus-maze tests in Thy1alpha6 mice, while being almost inactive in wild-type mice. The transgenic mice also lost quicker and for longer time their righting reflex after 25 mg/kg gaboxadol than wild-type mice. In hippocampal sections of Thy1alpha6 mice, the alpha6beta receptors could be visualized autoradiographically by interactions between gaboxadol and GABA via [(35)S]TBPS binding to the GABA(A) receptor ionophore. Gaboxadol inhibition of the binding could be partially prevented by GABA. Electrophysiology of recombinant GABA(A) receptors revealed that GABA was a partial Agonist at alpha6beta3 and alpha6beta3delta receptors, but a full Agonist at alpha6beta3gamma2 receptors when compared with gaboxadol. The results suggest strong behavioral effects via selective pharmacological activation of enriched extrasynaptic alphabeta GABA(A) receptors, and the mouse model represents an example of the functional consequences of altered balance between extrasynaptic and synaptic inhibition.