RGD Reference Report - Dopamine D4 receptor-mediated presynaptic inhibition of GABAergic transmission in the rat supraoptic nucleus. - Rat Genome Database

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Dopamine D4 receptor-mediated presynaptic inhibition of GABAergic transmission in the rat supraoptic nucleus.

Authors: Azdad, K  Piet, R  Poulain, DA  Oliet, SH 
Citation: Azdad K, etal., J Neurophysiol 2003 Aug;90(2):559-65. Epub 2003 Apr 23.
RGD ID: 1358607
Pubmed: PMID:12711714   (View Abstract at PubMed)
DOI: DOI:10.1152/jn.00226.2003   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dopamine receptor signaling pathway  IDA 1358607 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dopamine neurotransmitter receptor activity, coupled via Gi/Go  IDA 1358607 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd4  (dopamine receptor D4)


Additional Information