title: Accumbal noradrenaline that contributes to the alpha-adrenoceptor-mediated release of dopamine from reserpine-sensitive storage vesicles in the nucleus accumbens is derived from alpha-methyl-para-tyrosine-sensitive pools.
abstract: Alpha-adrenoceptors in the nucleus accumbens are known to inhibit accumbal dopamine release from reserpine-sensitive pools. The aim of this study was to test our previously reported hypothesis that accumbal noradrenaline that controls the dopamine release from these storage vesicles is derived from alpha-methyl-para-tyrosine-sensitive pools. The sensitivity of accumbal alpha-adrenoceptors to noradrenergic agents depends on the amount of noradrenaline that is available in the synapse. In case the synaptic noradrenaline levels decrease, the conformation of alpha-adrenoceptors changes into a state that makes these receptors more sensitive to its agonists. The effects of alpha-methyl-para-tyrosine, respectively reserpine, on the alpha-adrenoceptor-agonist-induced changes of accumbal dopamine release were investigated. Alpha-methyl-para-tyrosine, but not reserpine, made accumbal postsynaptic alpha-adrenoceptors more sensitive to phenylephrine. These results indicate that noradrenaline that inhibits the release of dopamine from reserpine-sensitive storage vesicles, via stimulation of accumbal postsynaptic alpha-adrenoceptors, is derived from alpha-methyl-para-tyrosine-sensitive pools. The clinical impact of these data is discussed.
authors.affiliation: Department of Cognitive Neuroscience, Division of Psychoneuropharmacology (PNF), Radboud University (RU) Nijmegen, Medical Centre, 6525 EZ, Nijmegen, The Netherlands. M.Verheij@cns.umcn.nl
authors.forename: M M M
authors.initials: MM
authors.lastname: Verheij
authors.forename: A R
authors.initials: AR
authors.lastname: Cools
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology*
chemical_list: D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D019805:alpha-Methyltyrosine; D012110:Reserpine; D004298:Dopamine; D009638:Norepinephrine