J Neurophysiol 90: 559-565, 2003.
First published April 23, 2003; doi:10.1152/jn.00226.2003
0022-3077/03 $5.00
Dopamine D4 Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in the Rat Supraoptic Nucleus
Karima Azdad,
Richard Piet,
Dominique A. Poulain and
Stéphane H. R. Oliet
Institut National de la Santé et de la Recherche Médicale
U.378, Université Victor Segalen, Institut François Magendie,
33077 Bordeaux, France
Submitted 10 March 2003;
accepted in final form 18 April 2003
The mechanism by which dopamine induces or facilitates neurohypophysial
hormone release is not completely understood. Because oxytocin- and
vasopressin-secreting supraoptic neurons are under the control of a prominent
GABAergic inhibition, we investigated the possibility that dopamine exerts its
action by modulating GABA-mediated transmission. Whole cell voltage-clamp
recordings of supraoptic neurons were carried out in acute hypothalamic slices
to determine the action of dopamine on inhibitory postsynaptic currents.
Application of dopamine caused a consistent and reversible reduction in the
frequency, but not the amplitude, of miniature synaptic events, indicating
that dopamine was acting presynaptically to reduce GABAergic transmission. The
subtype of dopamine receptor involved in this response was characterized
pharmacologically. Dopamine inhibitory action was greatly reduced by two
highly selective D4 receptor antagonists L745,870 and L750,667 and to a lower
extent by the antipsychotic drug clozapine but was unaffected by SCH 23390 and
sulpiride, D1/D5 and D2/D3 receptor antagonists, respectively. In agreement
with these results, the action of dopamine was mimicked by the potent D4
receptor agonist PD168077 but not by SKF81297 and bromocriptine, D1/D5 and
D2/D3 receptor agonists, respectively. Dopamine and PD168077 also reduced the
amplitude of evoked inhibitory postsynaptic currents, an effect that was
accompanied by an increase in paired-pulse facilitation. These data clearly
indicate that D4 receptors are located on GABA terminals in the supraoptic
nucleus and that their activation reduces GABA release in the supraoptic
nucleus. Therefore dopaminergic facilitation of neurohypophysial hormone
release appears to result, at least in part, from disinhibition of
magnocellular neurons caused by the depression of GABAergic transmission.
Address for reprint requests: S.H.R. Oliet, INSERM U378 - Institut
François Magendie, 1, rue Camille St-Saëns, 33077 Bordeaux Cedex,
France (E-mail:
stephane.oliet{at}bordeaux.inserm.fr).
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Copyright © 2003 by the The American Physiological Society.
