Abstract
We investigated by means of behavioral and neurochemical studies the effects of either D 1 or D 2 agonist on excessive dopamine release and hyperactivity induced by the microinjection of Bay K 8644, and an L-type Ca 2+ channel stimulant, into the rat caudate putamen under a novel environmental condition. Hyperactivity (locomotor activity and rearing counts) and significant increases in extracellular dopamine levels induced by Bay K 8644 were concomitantly observed. D 1 agonist, SKF81297, administered into the caudate putamen did not block Bay K 8644-induced hyperactivity measured by monitoring both animal activity and increases in extracellular dopamine levels detected by microdialysis. Pretreatment with the D 2 agonists, bromocriptine, talipexole and pramipexole, into the caudate putamen significantly blocked Bay K 8644-induced hyperactivity for 45 min after Bay K 8644 administration, although the single administration of these agonists significantly potentiated locomotor activity and rearing behavior. Furthermore, these agonists significantly suppressed Bay K 8644-induced extracellular dopamine levels. Our results indicate that these D 2 agonists (1) act on postsynaptic neuronal D 2 receptors under conditions of normal or low dopamine release in the caudate putamen, and (2) act on presynaptic D 2 receptors (autoreceptors) when excessive levels of dopamine are released or hyperdopamine neuronal activity is induced. Consequently, the effect of D 2 agonists in the clinical treatment of Parkinson’s disease may be due to stimulation of postsynaptic D 2 receptors rather than presynaptic autoreceptors.
Published Version
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