Dopamine D4 receptor activation inhibits presynaptically glutamatergic neurotransmission in the rat supraoptic nucleus.
Oxytocin and vasopressin release from magnocellular neurons of the supraoptic nucleus is under the control of glutamate-dependent excitation. The supraoptic nucleus also receives a generalized dopaminergic input from hypothalamic sources. To determine if dopamine can influence this excitatory drive onto the magnocellular neurons, we used whole-cell patch clamp to record the effect of dopamine on evoked and miniature excitatory postsynaptic currents in rat hypothalamic slices. Dopamine exposure (30 microM to 1 mM) induced a large and reversible reduction in the amplitude of evoked excitatory postsynaptic current in nearly all magnocellular cells tested. D4 receptors appeared to mediate dopamine's activity, based on inhibition of the response with 50 microM clozapine, but not by SCH 23390 or sulpiride, and mimicry of dopamine's action with the D4 specific agonist, PD 168077. Analysis of paired-pulse experiments and miniature postsynaptic currents indicated that dopamine's action involved a presynaptic mechanism, since the frequency of miniature postsynaptic currents was reduced with dopamine exposure without any change in current kinetics or amplitude, while the paired-pulse ratio increased. We therefore have demonstrated for the first time a role for dopamine D4 receptors in the supraoptic nucleus in the presynaptic inhibition of glutamatergic neurotransmission onto magnocellular neurons.
Price
C J
CJ
Neuroscience Research Group, Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr., Calgary, Alberta T2N 4N1, Canada. cprice@ucalgary.ca
Pittman
Q J
QJ
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D050638:Receptors, Dopamine D4; D013469:Sulpiride / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D001549:Benzamides; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D018756:GABA Antagonists; C103081:L 750667; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D018698:Glutamic Acid; C067113:SK&F 81297; D013469:Sulpiride; D003024:Clozapine; D004298:Dopamine