title: Alpha-1 adrenoreceptors modulate GABA release onto ventral tegmental area dopamine neurons.
abstract: 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; p < 0.05). Prazosin (1 μM, α1-AR antagonist), blocked this effect. Paired-pulse ratios were increased by phenylephrine application (n = 13; p < 0.05) indicating a presynaptic site of action. Spontaneous IPSCs frequency but not amplitude, were decreased in the presence of phenylephrine (n = 7; p < 0.05). However, frequency or amplitude of miniature IPSCs were not changed (n = 9; p > 0.05). Phenylephrine in low Ca(2+) (1 mM) medium decreased IPSC amplitude (n = 7; p < 0.05). Chelerythrine (a protein kinase C inhibitor) blocked the α1-AR action on IPSC amplitude (n = 6; p < 0.05). Phenylephrine failed to decrease IPSCs amplitude in the presence of paxilline, a BK channel blocker (n = 7; p < 0.05). 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.
authors.affiliation: Department of Physiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA; Laboratorio de Neurociencias y Comportamiento, Departamento de Ciencias Básicas, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Velásquez-Martínez
authors.affiliation: Department of Physiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vázquez-Torres
authors.affiliation: Department of Physiology, Universidad Central del Caribe, Bayamón, PR, USA.
authors.forename: Legier V
authors.initials: LV
authors.lastname: Rojas
authors.affiliation: Department of Physiology, Universidad Central del Caribe, Bayamón, PR, USA.
authors.forename: Priscila
authors.initials: P
authors.lastname: Sanabria
authors.affiliation: Department of Physiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA. Electronic address: carlos.jimenez8@upr.edu.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Jiménez-Rivera
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D046509:Tissue Culture Techniques; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D053119:Benzophenanthridines; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C048220:paxilline; D005680:gamma-Aminobutyric Acid; C016299:chelerythrine; D011493:Protein Kinase C; D011224:Prazosin
keywords: Alpha1-adrenoreceptor; Dopamine neurons; GABA release; Ventral tegmental area