D-1 receptor mediated modulation of the release of gamma-aminobutyric acid by endogenous dopamine in the basal ganglia of the rat

Prog Neuropsychopharmacol Biol Psychiatry. 1995 Sep;19(5):727-39. doi: 10.1016/0278-5846(95)00127-h.


1. Presynaptic D1 receptors are present on GABAergic terminals of neostriatal projections. 2. By activating these receptors, exogenous dopamine enhances the release of GABA. 3. Here the authors have explored whether endogenous dopamine was also able to activate the receptors, thus enhancing GABA release. 4. The effect of methamphetamine, a dopamine releaser, on the release of tritiated GABA was studied in slices of substantia nigra pars reticulata, entopeduncular nucleus and caudate-putamen, targets of the striatal projections. 5. Methamphetamine enhanced the release of the label. However the enhancement required an intact dopaminergic innervation, since it was lost in slices isolated from rats with 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system. 6. The activation of the receptors by endogenous dopamine was also judged by the effect of the selective D1 antagonist SCH 23390 in potassium depolarized slices. By preventing activation of the receptors by dopamine released as result of depolarization, the antagonist reduced GABA release. In 6-OHDA lesioned slices, no reduction was observed, even though the slices were also depolarized. 7. The results indicate that endogenous dopamine enhances GABA release from striatal terminals in the pars reticulata of the substantia nigra, entopeduncular nucleus and caudate-putamen. This would facilitate GABAergic neurotransmission. 8. The study suggests that the function of DA in the basal ganglia is widespread, modulating not only the firing of the striatal efferent neurons but also the transmission of the fired impulses across synapses in the target nuclei of these neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / metabolism*
  • Benzazepines / pharmacology
  • Dopamine / pharmacology*
  • Efferent Pathways / drug effects
  • Male
  • Methamphetamine / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / drug effects*
  • Receptors, Dopamine D1 / physiology*
  • Substantia Nigra / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • Benzazepines
  • Receptors, Dopamine D1
  • Methamphetamine
  • gamma-Aminobutyric Acid
  • Dopamine