Continuously infusing quinpirole decreases Ca2+/calmodulin-dependent phosphorylation in mouse striatum

Area of Science:

• Neuropharmacology
• Behavioral Neuroscience

Background:

• Dopamine receptors, particularly D2, play a crucial role in regulating motor behaviors.
• Continuous agonist stimulation can lead to receptor desensitization and behavioral adaptation.

Purpose of the Study:

• To investigate the biochemical mechanisms underlying the down-regulation of stereotypic behavior induced by chronic quinpirole administration.
• To examine changes in dopamine receptor density and protein phosphorylation in the mouse striatum.

Main Methods:

• Mice received continuous infusion of the D2 dopamine agonist quinpirole for 6 days.
• Striatal tissue was analyzed for D1 and D2 dopamine receptor levels.
• Activities of protein phosphorylation enzymes and levels of calmodulin-binding proteins were assessed.

Main Results:

• Chronic quinpirole administration led to a significant decrease in D2 dopamine receptors and a non-significant increase in D1 receptors, elevating the D1/D2 ratio.
• A significant reduction in Ca2+/calmodulin-dependent phosphorylation of striatal membranes was observed.
• No significant changes were found in cyclic AMP-dependent protein kinase or protein kinase C activity, nor in calmodulin-binding protein levels.

Conclusions:

• Behavioral down-regulation of stereotypic behavior by continuous D2 dopamine agonist treatment is associated with D2 receptor down-regulation.
• Decreased Ca2+/calmodulin-dependent phosphorylation of striatal membranes is another key biochemical event linked to this behavioral adaptation.