{153} revision 0 modified: 0-0-2007 0:0

PMID-8539419 Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

  • D1 is inhibitory (modulatory) on striatal neurons.
  • D1 cloned in 1990
  • D1 stimulates adenyl cyclase. (cAMP)
  • D1 activity shown to be necessary, but not sufficient, to generate long-term depression in striatal slices.
  • SKF 38393 was designed as a selective D1 receptor agonist; it has been available since the late 70's; it has nanomolar affinity for D1-R. SKF 38393 inhibits action potential discharge in striatal neurons as measued through response to intracellular current depolarizations.
  • striatal cells project to the substantia nigra.
  • alternate hypothesis: D1 activation on the striatonigral afferents to the ventral tegmental area (VTA) promotes GABA release.
    • recall that the VTA projects to the frontal/prefrontal cortex (PFC) via the mesocortical dopiminergic pathway. http://grad.uchc.edu/phdfaculty/antic.html There, DA synapese on spines of distal dendrites in juxtaposition with glutamergic synapses. this guy posits that these DA synapses are involved in the pathology of schizophrenia, and he uses optical techniques to measure the DA/Glu synapses.
    • VTA is just below the red nucleus in rats.
  • some people report that SKF 38393 potentiated depolarizing membrane responses to exogenous NMDA (agonist, excitotoxin).
  • they prefer the magnesium-dependent LTD pathway.
    • D1 receptor antagonist SCH 23390 prevented the generation of LTD in striatum. (Calabresi et al 1992).
    • in DA-depleted slices, LTD could be restored by the co-administration of D1 and D2 agonists.