ALPHA-1 ADRENORECEPTORS MODULATE GABA RELEASE ONTO VENTRAL TEGMENTAL AREA DOPAMINE NEURONS
| Autor: | Priscila Sanabria, Carlos A. Jiménez-Rivera, Rafael Vázquez-Torres, Maria Carolina Velasquez-Martinez, Legier V. Rojas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
BK channel medicine.medical_specialty Indoles Patch-Clamp Techniques Voltage clamp Presynaptic Terminals Inhibitory postsynaptic potential Article Rats Sprague-Dawley Tissue Culture Techniques Cellular and Molecular Neuroscience chemistry.chemical_compound Phenylephrine Adrenergic Agents Dopamine Internal medicine Receptors Adrenergic alpha-1 medicine Potassium Channel Blockers Animals Large-Conductance Calcium-Activated Potassium Channels Paxilline Protein Kinase Inhibitors Protein Kinase C gamma-Aminobutyric Acid Pharmacology Benzophenanthridines biology Chemistry GABAA receptor Dopaminergic Neurons Miniature Postsynaptic Potentials Ventral Tegmental Area Prazosin Electric Stimulation Ventral tegmental area Endocrinology medicine.anatomical_structure Inhibitory Postsynaptic Potentials biology.protein Neuroscience medicine.drug |
| Popis: | The ventral tegmental area (VTA) plays an important role in reward and motivational processes involved in drug addiction. Previous studies have shown that alpha1-adrenoreceptors (α1-AR) are primarily found pre-synaptically at this area. We hypothesized that GABA released onto VTA-dopamine (DA) cells is modulated by pre-synaptic α1-AR. Recordings were obtained from putative VTA-DA cells of male Sprague-Dawley rats (28-50 days postnatal) using whole-cell voltage clamp technique. Phenylephrine (10 μM; α1-AR agonist) decreased the amplitude of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked by electrical stimulation of afferent fibers (n = 7; p0.05). Prazosin (1 μM, α1-AR antagonist), blocked this effect. Paired-pulse ratios were increased by phenylephrine application (n = 13; p0.05) indicating a presynaptic site of action. Spontaneous IPSCs frequency but not amplitude, were decreased in the presence of phenylephrine (n = 7; p0.05). However, frequency or amplitude of miniature IPSCs were not changed (n = 9; p0.05). Phenylephrine in low Ca(2+) (1 mM) medium decreased IPSC amplitude (n = 7; p0.05). Chelerythrine (a protein kinase C inhibitor) blocked the α1-AR action on IPSC amplitude (n = 6; p0.05). Phenylephrine failed to decrease IPSCs amplitude in the presence of paxilline, a BK channel blocker (n = 7; p0.05). Taken together, these results demonstrate that α1-ARs at presynaptic terminals can modulate GABA release onto VTA-DA cells. Drug-induced changes in α1-AR could contribute to the modifications occurring in the VTA during the addiction process. |
| Databáze: | OpenAIRE |
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