Dopaminergic behaviors and signal transduction mediated through adenylate cyclase and phospholipase C pathways.

Journal Article (Journal Article)

We determined the relative effects of chemical receptor inactivation on dopaminergic signaling through adenylate cyclase and phospholipase C pathways and evaluated the behavioral implications of such receptor manipulations. Groups of rats were given intraperitoneal injections of 10 mg/kg N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a reagent that differentially inactivates neurotransmitter receptors. Control and treated animals were used to assess dopaminergic-mediated behaviors or brain tissues were prepared from the animals and used to assay D1-like receptor binding and agonist-stimulated second messenger formation. EEDQ decreased by 75% the number of D1-like binding sites and completely abolished dopamine-stimulated cyclic AMP formation in striatal membranes. Conversely, dopamine-stimulated phosphoinositide hydrolysis was insensitive to inactivation by EEDQ as examined over different durations of EEDQ treatment, in different brain regions, or with different concentrations of the D1-like receptor agonist SKF38393. EEDQ-pretreated animals lost their stereotypic response to apomorphine but showed increased vacuous jaw movements in response to apomorphine or SKF38393. Basal catalepsy was increased and SCH23390 was unable to further enhance catalepsy beyond the basal levels in the lesioned animals. In naive animals, SCH23390 catalepsy was reversed by apomorphine, and apomorphine stereotypy was reversed by SCH23390. Taken together, the present results imply that the dopamine-sensitive phospholipase C system mediates a subset of dopaminergic behaviors, notably vacuous jaw movements, in contrast to stereotypy and catalepsy which appear to be respectively mediated through stimulation and inhibition of the adenylate cyclase-coupled dopaminergic system.

Full Text

Duke Authors

Cited Authors

  • Undie, AS; Berki, AC; Beardsley, K

Published Date

  • January 2000

Published In

Volume / Issue

  • 39 / 1

Start / End Page

  • 75 - 87

PubMed ID

  • 10665821

Electronic International Standard Serial Number (EISSN)

  • 1873-7064

International Standard Serial Number (ISSN)

  • 0028-3908

Digital Object Identifier (DOI)

  • 10.1016/s0028-3908(99)00106-9


  • eng