In vivo partial inactivation of dopamine D1 receptors induces hypersensitivity of cortical dopamine-sensitive adenylate cyclase: permissive role of alpha 1-adrenergic receptors

J Neurochem. 1992 Jul;59(1):331-7. doi: 10.1111/j.1471-4159.1992.tb08908.x.


As shown by autoradiography, peripheral injections of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) induced a dose-dependent decrease of [3H]SCH 23390 and [3H]prazosin high-affinity binding sites in the rat prefrontal cortex. EEDQ showed similar efficacy in inactivating cortical and striatal dopamine (DA) D1 receptors, whereas prazosin-sensitive alpha 1-adrenergic receptors were more sensitive to the action of the alkylating agent, as for all doses of EEDQ tested (from 0.8 to 3 mg/kg, i.p.), the decrease in cortical [3H]SCH 23390 binding was less pronounced than that of [3H]prazosin. The effects of EEDQ on [3H]SCH 23390 binding and DA-sensitive adenylate cyclase activity were then simultaneously compared in individual rats. In the striatum, whatever the dose of EEDQ used, the decrease of DA-sensitive adenylate cyclase activity was always lower than that of D1 binding sites, suggesting the occurrence of a large proportion of spare D1 receptors. In the prefrontal cortex, a significant increase in DA-sensitive adenylate cyclase activity was observed in rats treated with a low dose of EEDQ (0.8 mg/kg), this effect being associated with a slight reduction in [3H]SCH 23390 binding sites (-20%). Parallel decreases in the enzyme activity and D1 binding sites were observed with higher doses. The EEDQ-induced supersensitivity of DA-sensitive adenylate cyclase did not occur in rats in which the decrease in [3H]prazosin binding sites was higher than 35%.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Autoradiography
  • Benzazepines / metabolism
  • Binding Sites / drug effects
  • Corpus Striatum / enzymology*
  • Dopamine / pharmacology*
  • Drug Resistance
  • Frontal Lobe / enzymology*
  • Male
  • Prazosin / pharmacology
  • Quinolines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / physiology*
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / physiology*
  • Receptors, Dopamine D1


  • Adrenergic alpha-Antagonists
  • Benzazepines
  • Quinolines
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • EEDQ
  • Adenylyl Cyclases
  • Dopamine
  • Prazosin