Dopamine D4 receptor activation inhibits presynaptically glutamatergic neurotransmission in the rat supraoptic nucleus

Oxytocin and vasopressin release from magnocellular neurons of the supraopt ic nucleus is under the control of glutamate-dependent excitation. The supr aoptic nucleus also receives a generalized dopaminergic input from hypothal amic sources. To determine if dopamine can influence this excitatory drive onto the magnocellular neurons, we used whole-cell patch clamp to record th e effect of dopamine on evoked and miniature excitatory postsynaptic curren ts in rat hypothalamic slices. Dopamine exposure (30 muM to 1 mM) induced a large and reversible reduction in the amplitude of evoked excitatory posts ynaptic current in nearly all magnocellular cells tested. D4 receptors appe ared to mediate dopamine's activity, based on inhibition of the response wi th 50 muM clozapine, but not by SCH 23390 or sulpiride, and mimicry of dopa mine's action with the D4 specific agonist, PD 168077. Analysis of paired-p ulse experiments and miniature postsynaptic currents indicated that dopamin e's action involved a presynaptic mechanism, since the frequency of miniatu re postsynaptic currents was reduced with dopamine exposure without any cha nge in current kinetics or amplitude, while the paired-pulse ratio increase d. We therefore have demonstrated for the first time a role for dopamine D4 receptors in the supraoptic nucleus in the presynaptic inhibition of gluta matergic neurotransmission onto magnocellular neurons.