Nanomolar Concentrations of Pregnenolone Sulfate Enhance Striatal Dopamine Overflow In Vivo
| Autor: | David H. Farb, R. C. Pierce, G. C. Janis, Ghazaleh Sadri-Vakili, Terrell T. Gibbs |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Microdialysis
N-Methylaspartate medicine.drug_class Dopamine Biology Pharmacology Article chemistry.chemical_compound medicine Animals Receptors sigma Dose-Response Relationship Drug GABAA receptor Glutamate receptor Receptor antagonist Corpus Striatum Rats chemistry Pregnenolone Molecular Medicine NMDA receptor Pregnenolone sulfate Ionotropic effect medicine.drug Signal Transduction |
| Popis: | The balance between GABA-mediated inhibitory and glutamate-mediated excitatory synaptic transmission represents a fundamental mechanism for controlling nervous system function, and modulators that can alter this balance may participate in the pathophysiology of neuropsychiatric disorders. Pregnenolone sulfate (PS) is a neuroactive steroid that can modulate the activity of ionotropic glutamate and GABA(A) receptors either positively or negatively, depending upon the particular receptor subtype, and modulates synaptic transmission in a variety of experimental systems. To evaluate the modulatory effect of PS in vivo, we infused PS into rat striatum for 20 min via a microdialysis probe while monitoring local extracellular dopamine (DA) levels. The results demonstrate that PS at low nanomolar concentrations significantly increases extracellular DA levels. The PS-induced increase in extracellular DA is antagonized by the N-methyl-d-aspartate (NMDA) receptor antagonist, d-AP5 [d-(-)-2-amino-5-phosphonopentanoic acid], but not by the sigma receptor antagonist, BD 1063 [1(-)[2-(3,4-dichlorophenyl)-ethyl]-4-methylpiperazine]. The results demonstrate that exogenous PS, at nanomolar concentrations, is able to increase DA overflow in the striatum through an NMDA receptor-mediated pathway. |
| Databáze: | OpenAIRE |
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