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The D 1 Agonist Dihydrexidine Releases Acetylcholine and Improves Cognition in Rats
Author(s) -
STEELE T. D.,
HODGES D. B.,
LEVESQUE T. R.,
LOCKE K. W.,
SANDAGE B. W.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb34457.x
Subject(s) - agonist , acetylcholine , cognition , chemistry , neuroscience , pharmacology , acetylcholine receptor , medicine , psychology , receptor , biochemistry
Neurochemical and behavioral studies have elucidated extensive interactions between dopaminergic and cholinergic systems in brain areas associated with movement and cognition. The initial goal of these studies was to evaluate the effect of the anti‐Parkinson drug dihydrexidine (DHX), a dopamine D 1 full‐efficacy agonist, on brain acetylcholine (ACh) release using in vivo microdialysis techniques. Moderate doses of DHX (3 and 10 mg/kg) produced approximately a 50% increase in striatal ACh release that was blocked by the D 1 agonist SCH23390 (0.3 mg/kg). A higher dose of DHX (17.5 mg/kg) was less effective in raising striatal ACh, possibly due to D 2 receptor activation. In frontal cortex, DHX (10 mg/kg) evoked a more robust increase in ACh release (+ 200%) that was blocked by SCH23390 (0.3 mg/kg). Since elevations in brain ACh are associated with cognitive improvement, the effectiveness of DHX in a passive avoidance model of learning and memory was also evaluated. These studies revealed a significant improvement in performance by 0.3 mg/kg DHX in scopolamine‐induced amnestic rats. These results provided support for the hypothesis that DHX improves cognitive performance as a consequence of ACh release in relevant brain regions. Further, D 1 agonists may have novel therapeutic potential in the treatment of dementia.