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.