title: A Role for Adenosine A1 Receptors in GABA and NMDA-Receptor Mediated Modulation of Dopamine Release: Studies Using Fast Cyclic Voltammetry.
abstract: In the striatum many neurotransmitters including GABA, glutamate, acetylcholine, dopamine, nitric oxide and adenosine interact to regulate synaptic transmission. Dopamine release in the striatum is regulated by a number of pre- and postsynaptic receptors including adenosine. We have recently shown using isolated rat striatal slices, and the technique of fast cyclic voltammetry, that adenosine A1 receptor-mediated inhibition of dopamine release is modulated by dopamine D1 receptors. In the present study we have investigated the influence of NMDA and GABA receptor activation on the modulation of electrically stimulated dopamine release by adenosine. Application of the adenosine A1 receptor agonist, N⁶-cyclopentyladenosine (CPA), concentration-dependently inhibited dopamine release to a maxiumum of 50%. Perfusion of the glutamate receptor agonist, NMDA, in low magnesium, caused a rapid and concentration-dependent inhibition of dopamine release. Prior perfusion with the adenosine A₁ receptor antagonist, DPCPX, significantly reduced the effect of 5 mM and 10 mM NMDA on dopamine release. The GABAAreceptor agonist, isoguvacine, had a significant concentration-dependent inhibitory effect on dopamine release which was reversed by prior application of the GABAAreceptor antagonist, picrotoxin, but not DPCPX. Finally inhibition of dopamine release by CPA (1mM) was significantly enhanced by prior perfusion with picrotoxin. These data demonstrate an important role for GABA, NMDA and adenosine in the modulation of dopamine release.
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. john.oconnor@ucd.ie.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Connor
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Carmel
authors.initials: C
authors.lastname: O'Neill
keywords: Adenosine; Fast cyclic voltammetry; GABA; NMDA; dorsolateral striatum