D1 agonist dihydrexidine releases acetylcholine and improves cognitive performance in rats.

Abstract

Dihydrexidine is a selective, full-efficacy dopamine D1 receptor agonist that has displayed therapeutic potential in Parkinson's disease by reversing motor deficits of MPTP-treated monkeys. The present study monitored the effects of dihydrexidine on acetylcholine release in rat brain by using in vivo microdialysis. Moderate doses of dihydrexidine [3 and 10 mg/kg, intraperitoneally (I.P.)] elevated extracellular concentrations of acetylcholine by 40-60% in rat striatum; higher doses did not significantly alter acetylcholine release. SCH 23390 blocked the dihydrexidine-induced increase, indicating a D1 receptor-mediated action. A more robust stimulatory effect of dihydrexidine on acetylcholine release was observed in prefrontal cortex (to 300% of basal output) than in striatum. Dihydrexidine was also evaluated in a passive avoidance procedure in rats to determine if its neurochemical effects translated into cognition-enhancing activity; in this assay, dihydrexidine (0.3 mg/kg, I.P.) significantly improved the scopolamine-induced deficits. The results of these studies suggest that the acetylcholine-releasing properties of dihydrexidine and other D1 agonists may underlie their cognition-enhancing activity and thus may have clinical value in the treatment of dementia.

• Authors: T D Steele, D B Hodges Jr, T R Levesque, K W Locke
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 58 Issue 2 Pg. 477-83 (Oct 1997) ISSN: 0091-3057 [Print] United States
• PMID: 9300608 (Publication Type: Journal Article)

Chemical References

• Dopamine Agonists
• Phenanthridines
• dihydrexidine
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Animals
• Avoidance Learning (drug effects)
• Cognition (drug effects)
• Dopamine Agonists (pharmacology)
• Dose-Response Relationship, Drug
• Male
• Microdialysis
• Phenanthridines (pharmacology)
• Rats
• Rats, Sprague-Dawley