Dopamine Modulation of Membrane Excitability in Striatal Spiny Neurons is Altered in DARPP-32 Knockout Mice
| Autor: | Anthony A. Grace, Shao-Pii Onn, Allen A. Fienberg |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Agonist Dopamine and cAMP-Regulated Phosphoprotein 32 medicine.medical_specialty medicine.drug_class Dopamine Nerve Tissue Proteins Stimulation Striatum In Vitro Techniques Biology Medium spiny neuron Mice Dopamine receptor D1 Internal medicine medicine Animals Mice Knockout Neurons Pharmacology Receptors Dopamine D2 Receptors Dopamine D1 Cell Membrane Phosphoproteins Corpus Striatum Endocrinology Rheobase Knockout mouse Molecular Medicine 2 3 4 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 306:870-879 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.103.050062 |
| Popis: | The phosphoprotein DARPP-32 (dopamine and cAMP-regulated phosphoprotein 32 kDa) plays a central role in mediating the actions of a variety of neurotransmitters in medium spiny neurons of the striatum (Greengard, 1990; Fienberg et al., 1998). This study examines D1 and D2 dopamine (DA) agonist effects on the membrane properties of identified striatal neurons recorded in slices obtained from wild-type and DARPP-32-knockout mice. In wild-type spiny cells, DA D1 receptor activation decreased cell excitability, causing a 58.8 ± 13.5% increase in rheobase current required to evoke spike discharge. In contrast, D1 agonist administration did not alter cell excitability when applied to spiny cells in slices prepared from the DARPP-32 knockout mice. D2 agonist administration decreased cell excitability in both wild-type and knockout mice. The response produced by combined D1 and D2 agonist stimulation was dependent on the sequence of agonist administration. Thus, the D1 agonist-induced decrease in excitability was reversed to a facilitation of spiking upon subsequent D2 agonist administration. In contrast, D2 agonist applied simultaneously with the D1 agonist only produced a reduction in excitability. This type of D1-dependent modulation was not present in slices from the DARPP-32 knockout mice. |
| Databáze: | OpenAIRE |
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