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Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells.
Neuroscience. 2012 Aug 02; 216:18-30.N

Abstract

The ventral tegmental area (VTA) plays an important role in reward and motivational processes that facilitate the development of drug addiction. Glutamatergic inputs into the VTA contribute to dopamine (DA) neuronal activation related to reward and response-initiating effects in drug abuse. Previous investigations indicate that alpha1-adrenoreceptors (α1-ARs) are primarily localized at presynaptic elements in the ventral midbrain. Studies from several brain regions have shown that presynaptic α1-AR activation enhances glutamate release. Therefore, we hypothesized that glutamate released onto VTA-DA neurons 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 voltage clamp techniques. Phenylephrine (10 μM) and methoxamine (80μM), both α1-AR agonists, increased AMPA receptor-mediated excitatory postsynaptic currents' (EPSCs) amplitude evoked by electrical stimulation of afferent fibers (p<0.05). This effect was blocked by the α1-AR antagonist prazosin (1 μM). Phenylephrine decreased the paired-pulse ratio (PPR) and increased spontaneous EPSCs' frequencies but not their amplitudes suggesting a presynaptic locus of action. No changes in miniature EPSCs (0.5μM, tetrodotoxin [TTX]) were observed after phenylephrine's application which suggests that α1-AR effect was action potential dependent. Normal extra- and intracellular Ca(2+) concentration seems necessary for the α1-AR effect since phenylephrine in low Ca(2+) artificial cerebrospinal fluid (ACSF) and depletion of intracellular Ca(2+) stores with thapsigargin (10 μM) failed to increase the AMPA EPSCs' amplitude. Chelerythrine (1μM, protein kinase C (PKC) inhibitor) but not Rp-cAMPS (11 μM, PKA inhibitor) blocked the α1-AR activation effect on AMPA EPSCs, indicating that a PKC intracellular pathway is required. These results demonstrated that presynaptic α1-AR activation modulates glutamatergic inputs that affect VTA-DA neuronal excitability. α1-AR action might be heterosynaptically localized at glutamatergic fibers terminating onto VTA-DA neurons. It is suggested that drug-induced changes in α1-AR could be part of the neuroadaptations occurring in the mesocorticolimbic circuitry during the addiction process.

Authors+Show Affiliations

Department of Physiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22542873

Citation

Velásquez-Martinez, M C., et al. "Activation of Alpha1-adrenoceptors Enhances Glutamate Release Onto Ventral Tegmental Area Dopamine Cells." Neuroscience, vol. 216, 2012, pp. 18-30.
Velásquez-Martinez MC, Vázquez-Torres R, Jiménez-Rivera CA. Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells. Neuroscience. 2012;216:18-30.
Velásquez-Martinez, M. C., Vázquez-Torres, R., & Jiménez-Rivera, C. A. (2012). Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells. Neuroscience, 216, 18-30. https://doi.org/10.1016/j.neuroscience.2012.03.056
Velásquez-Martinez MC, Vázquez-Torres R, Jiménez-Rivera CA. Activation of Alpha1-adrenoceptors Enhances Glutamate Release Onto Ventral Tegmental Area Dopamine Cells. Neuroscience. 2012 Aug 2;216:18-30. PubMed PMID: 22542873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells. AU - Velásquez-Martinez,M C, AU - Vázquez-Torres,R, AU - Jiménez-Rivera,C A, Y1 - 2012/04/24/ PY - 2011/09/29/received PY - 2012/03/09/revised PY - 2012/03/16/accepted PY - 2012/5/1/entrez PY - 2012/5/1/pubmed PY - 2012/10/18/medline SP - 18 EP - 30 JF - Neuroscience JO - Neuroscience VL - 216 N2 - The ventral tegmental area (VTA) plays an important role in reward and motivational processes that facilitate the development of drug addiction. Glutamatergic inputs into the VTA contribute to dopamine (DA) neuronal activation related to reward and response-initiating effects in drug abuse. Previous investigations indicate that alpha1-adrenoreceptors (α1-ARs) are primarily localized at presynaptic elements in the ventral midbrain. Studies from several brain regions have shown that presynaptic α1-AR activation enhances glutamate release. Therefore, we hypothesized that glutamate released onto VTA-DA neurons 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 voltage clamp techniques. Phenylephrine (10 μM) and methoxamine (80μM), both α1-AR agonists, increased AMPA receptor-mediated excitatory postsynaptic currents' (EPSCs) amplitude evoked by electrical stimulation of afferent fibers (p<0.05). This effect was blocked by the α1-AR antagonist prazosin (1 μM). Phenylephrine decreased the paired-pulse ratio (PPR) and increased spontaneous EPSCs' frequencies but not their amplitudes suggesting a presynaptic locus of action. No changes in miniature EPSCs (0.5μM, tetrodotoxin [TTX]) were observed after phenylephrine's application which suggests that α1-AR effect was action potential dependent. Normal extra- and intracellular Ca(2+) concentration seems necessary for the α1-AR effect since phenylephrine in low Ca(2+) artificial cerebrospinal fluid (ACSF) and depletion of intracellular Ca(2+) stores with thapsigargin (10 μM) failed to increase the AMPA EPSCs' amplitude. Chelerythrine (1μM, protein kinase C (PKC) inhibitor) but not Rp-cAMPS (11 μM, PKA inhibitor) blocked the α1-AR activation effect on AMPA EPSCs, indicating that a PKC intracellular pathway is required. These results demonstrated that presynaptic α1-AR activation modulates glutamatergic inputs that affect VTA-DA neuronal excitability. α1-AR action might be heterosynaptically localized at glutamatergic fibers terminating onto VTA-DA neurons. It is suggested that drug-induced changes in α1-AR could be part of the neuroadaptations occurring in the mesocorticolimbic circuitry during the addiction process. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/22542873/Activation_of_alpha1_adrenoceptors_enhances_glutamate_release_onto_ventral_tegmental_area_dopamine_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(12)00337-5 DB - PRIME DP - Unbound Medicine ER -