Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex
Psychostimulant addiction is associated with dysfunctions in frontal cortex. Previous data demonstrated that repeated exposure to methamphetamine (METH) can alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal from repetitive non-contingent METH administration (7 days, 1...
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13556215_v21_n3_p589_Gonzalez http://hdl.handle.net/20.500.12110/paper_13556215_v21_n3_p589_Gonzalez |
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paper:paper_13556215_v21_n3_p589_Gonzalez2025-07-30T18:47:00Z Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex Dopamine receptors glutamate methamphetamine prefrontal cortex voltage-gated calcium channels 8 chloro 2,3,4,5 tetrahydro 3 methyl 5 phenyl 1h 3 benzazepin 7 ol hydrogen maleate AMPA receptor calcium channel N type calcium channel P type calcium channel Q type calcium channel T type cyclic nucleotide gated channel dopamine 1 receptor dopamine 5 receptor messenger RNA metabotropic receptor methamphetamine n methyl dextro aspartic acid receptor AMPA receptor benzazepine derivative Cacna1b protein, mouse Cacna1g protein, mouse Cacna1h protein, mouse Cacna1i protein, mouse CACNA2D1 protein, mouse calcium calcium channel calcium channel N type calcium channel T type dopamine 1 receptor dopamine 5 receptor dopamine uptake inhibitor glutamate receptor ionotropic, AMPA 1 Gprin1 protein, mouse Hcn1 protein, mouse Hcn2 protein, mouse hyperpolarization activated cyclic nucleotide gated channel messenger RNA methamphetamine n methyl dextro aspartic acid receptor nerve protein potassium channel voltage-dependent calcium channel (P-Q type) animal experiment animal model animal tissue Article Cacna1a gene Cacna1b gene Cacna1g gene Cacna1h gene Cacna1i gene Cacna2d1 gene calcium current controlled study excitatory postsynaptic potential gene gene expression Gria1 gene Grin1 gene Hcn1 gene Hcn2 gene hyperpolarization in vitro study male medial prefrontal cortex methamphetamine dependence mouse nonhuman priority journal synaptic transmission animal antagonists and inhibitors drug effects genetics metabolism prefrontal cortex pyramidal nerve cell Animals Benzazepines Calcium Calcium Channels Calcium Channels, N-Type Calcium Channels, T-Type Dopamine Uptake Inhibitors Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Male Methamphetamine Mice Nerve Tissue Proteins Potassium Channels Prefrontal Cortex Pyramidal Cells Receptors, AMPA Receptors, Dopamine D1 Receptors, Dopamine D5 Receptors, N-Methyl-D-Aspartate RNA, Messenger Synaptic Transmission Psychostimulant addiction is associated with dysfunctions in frontal cortex. Previous data demonstrated that repeated exposure to methamphetamine (METH) can alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal from repetitive non-contingent METH administration (7 days, 1 mg/kg) depressed voltage-dependent calcium currents (ICa) and increased hyperpolarization-activated cation current (IH) amplitude and the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) in deep-layer pyramidal mPFC neurons. Most of these effects were blocked by systemic co-administration of the D1/D5 receptor antagonist SCH23390 (0.5 and 0.05 mg/kg). In vitroMETH (i.e. bath-applied to slices from naïve-treated animals) was able to emulate its systemic effects on ICa and evoked EPSCs paired-pulse ratio. We also provide evidence of altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Cav2.1), N-type Cacna1b (Cav2.2), T-type Cav3.1 Cacna1g, Cav3.2 Cacna1h, Cav3.3 Cacna1i and the auxiliary subunit Cacna2d1 (α2δ1); (2) hyperpolarization-activated cyclic nucleotide-gated channels Hcn1 and Hcn2; and (3) glutamate receptors subunits AMPA-type Gria1, NMDA-type Grin1 and metabotropic Grm1 in the mouse mPFC after repeated METH treatment. Moreover, we show that some of these changes in mRNA expression were sensitive D1/5 receptor blockade. Altogether, these altered mechanisms affecting synaptic physiology and transcriptional regulation may underlie PFC functional alterations that could lead to PFC impairments observed in METH-addicted individuals. © 2015 Society for the Study of Addiction. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13556215_v21_n3_p589_Gonzalez http://hdl.handle.net/20.500.12110/paper_13556215_v21_n3_p589_Gonzalez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Dopamine receptors glutamate methamphetamine prefrontal cortex voltage-gated calcium channels 8 chloro 2,3,4,5 tetrahydro 3 methyl 5 phenyl 1h 3 benzazepin 7 ol hydrogen maleate AMPA receptor calcium channel N type calcium channel P type calcium channel Q type calcium channel T type cyclic nucleotide gated channel dopamine 1 receptor dopamine 5 receptor messenger RNA metabotropic receptor methamphetamine n methyl dextro aspartic acid receptor AMPA receptor benzazepine derivative Cacna1b protein, mouse Cacna1g protein, mouse Cacna1h protein, mouse Cacna1i protein, mouse CACNA2D1 protein, mouse calcium calcium channel calcium channel N type calcium channel T type dopamine 1 receptor dopamine 5 receptor dopamine uptake inhibitor glutamate receptor ionotropic, AMPA 1 Gprin1 protein, mouse Hcn1 protein, mouse Hcn2 protein, mouse hyperpolarization activated cyclic nucleotide gated channel messenger RNA methamphetamine n methyl dextro aspartic acid receptor nerve protein potassium channel voltage-dependent calcium channel (P-Q type) animal experiment animal model animal tissue Article Cacna1a gene Cacna1b gene Cacna1g gene Cacna1h gene Cacna1i gene Cacna2d1 gene calcium current controlled study excitatory postsynaptic potential gene gene expression Gria1 gene Grin1 gene Hcn1 gene Hcn2 gene hyperpolarization in vitro study male medial prefrontal cortex methamphetamine dependence mouse nonhuman priority journal synaptic transmission animal antagonists and inhibitors drug effects genetics metabolism prefrontal cortex pyramidal nerve cell Animals Benzazepines Calcium Calcium Channels Calcium Channels, N-Type Calcium Channels, T-Type Dopamine Uptake Inhibitors Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Male Methamphetamine Mice Nerve Tissue Proteins Potassium Channels Prefrontal Cortex Pyramidal Cells Receptors, AMPA Receptors, Dopamine D1 Receptors, Dopamine D5 Receptors, N-Methyl-D-Aspartate RNA, Messenger Synaptic Transmission |
| spellingShingle |
Dopamine receptors glutamate methamphetamine prefrontal cortex voltage-gated calcium channels 8 chloro 2,3,4,5 tetrahydro 3 methyl 5 phenyl 1h 3 benzazepin 7 ol hydrogen maleate AMPA receptor calcium channel N type calcium channel P type calcium channel Q type calcium channel T type cyclic nucleotide gated channel dopamine 1 receptor dopamine 5 receptor messenger RNA metabotropic receptor methamphetamine n methyl dextro aspartic acid receptor AMPA receptor benzazepine derivative Cacna1b protein, mouse Cacna1g protein, mouse Cacna1h protein, mouse Cacna1i protein, mouse CACNA2D1 protein, mouse calcium calcium channel calcium channel N type calcium channel T type dopamine 1 receptor dopamine 5 receptor dopamine uptake inhibitor glutamate receptor ionotropic, AMPA 1 Gprin1 protein, mouse Hcn1 protein, mouse Hcn2 protein, mouse hyperpolarization activated cyclic nucleotide gated channel messenger RNA methamphetamine n methyl dextro aspartic acid receptor nerve protein potassium channel voltage-dependent calcium channel (P-Q type) animal experiment animal model animal tissue Article Cacna1a gene Cacna1b gene Cacna1g gene Cacna1h gene Cacna1i gene Cacna2d1 gene calcium current controlled study excitatory postsynaptic potential gene gene expression Gria1 gene Grin1 gene Hcn1 gene Hcn2 gene hyperpolarization in vitro study male medial prefrontal cortex methamphetamine dependence mouse nonhuman priority journal synaptic transmission animal antagonists and inhibitors drug effects genetics metabolism prefrontal cortex pyramidal nerve cell Animals Benzazepines Calcium Calcium Channels Calcium Channels, N-Type Calcium Channels, T-Type Dopamine Uptake Inhibitors Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Male Methamphetamine Mice Nerve Tissue Proteins Potassium Channels Prefrontal Cortex Pyramidal Cells Receptors, AMPA Receptors, Dopamine D1 Receptors, Dopamine D5 Receptors, N-Methyl-D-Aspartate RNA, Messenger Synaptic Transmission Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| topic_facet |
Dopamine receptors glutamate methamphetamine prefrontal cortex voltage-gated calcium channels 8 chloro 2,3,4,5 tetrahydro 3 methyl 5 phenyl 1h 3 benzazepin 7 ol hydrogen maleate AMPA receptor calcium channel N type calcium channel P type calcium channel Q type calcium channel T type cyclic nucleotide gated channel dopamine 1 receptor dopamine 5 receptor messenger RNA metabotropic receptor methamphetamine n methyl dextro aspartic acid receptor AMPA receptor benzazepine derivative Cacna1b protein, mouse Cacna1g protein, mouse Cacna1h protein, mouse Cacna1i protein, mouse CACNA2D1 protein, mouse calcium calcium channel calcium channel N type calcium channel T type dopamine 1 receptor dopamine 5 receptor dopamine uptake inhibitor glutamate receptor ionotropic, AMPA 1 Gprin1 protein, mouse Hcn1 protein, mouse Hcn2 protein, mouse hyperpolarization activated cyclic nucleotide gated channel messenger RNA methamphetamine n methyl dextro aspartic acid receptor nerve protein potassium channel voltage-dependent calcium channel (P-Q type) animal experiment animal model animal tissue Article Cacna1a gene Cacna1b gene Cacna1g gene Cacna1h gene Cacna1i gene Cacna2d1 gene calcium current controlled study excitatory postsynaptic potential gene gene expression Gria1 gene Grin1 gene Hcn1 gene Hcn2 gene hyperpolarization in vitro study male medial prefrontal cortex methamphetamine dependence mouse nonhuman priority journal synaptic transmission animal antagonists and inhibitors drug effects genetics metabolism prefrontal cortex pyramidal nerve cell Animals Benzazepines Calcium Calcium Channels Calcium Channels, N-Type Calcium Channels, T-Type Dopamine Uptake Inhibitors Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Male Methamphetamine Mice Nerve Tissue Proteins Potassium Channels Prefrontal Cortex Pyramidal Cells Receptors, AMPA Receptors, Dopamine D1 Receptors, Dopamine D5 Receptors, N-Methyl-D-Aspartate RNA, Messenger Synaptic Transmission |
| description |
Psychostimulant addiction is associated with dysfunctions in frontal cortex. Previous data demonstrated that repeated exposure to methamphetamine (METH) can alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal from repetitive non-contingent METH administration (7 days, 1 mg/kg) depressed voltage-dependent calcium currents (ICa) and increased hyperpolarization-activated cation current (IH) amplitude and the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) in deep-layer pyramidal mPFC neurons. Most of these effects were blocked by systemic co-administration of the D1/D5 receptor antagonist SCH23390 (0.5 and 0.05 mg/kg). In vitroMETH (i.e. bath-applied to slices from naïve-treated animals) was able to emulate its systemic effects on ICa and evoked EPSCs paired-pulse ratio. We also provide evidence of altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Cav2.1), N-type Cacna1b (Cav2.2), T-type Cav3.1 Cacna1g, Cav3.2 Cacna1h, Cav3.3 Cacna1i and the auxiliary subunit Cacna2d1 (α2δ1); (2) hyperpolarization-activated cyclic nucleotide-gated channels Hcn1 and Hcn2; and (3) glutamate receptors subunits AMPA-type Gria1, NMDA-type Grin1 and metabotropic Grm1 in the mouse mPFC after repeated METH treatment. Moreover, we show that some of these changes in mRNA expression were sensitive D1/5 receptor blockade. Altogether, these altered mechanisms affecting synaptic physiology and transcriptional regulation may underlie PFC functional alterations that could lead to PFC impairments observed in METH-addicted individuals. © 2015 Society for the Study of Addiction. |
| title |
Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| title_short |
Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| title_full |
Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| title_fullStr |
Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| title_full_unstemmed |
Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| title_sort |
methamphetamine blunts ca2+ currents and excitatory synaptic transmission through d1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13556215_v21_n3_p589_Gonzalez http://hdl.handle.net/20.500.12110/paper_13556215_v21_n3_p589_Gonzalez |
| _version_ |
1840327753009725440 |