A QUANTITATIVE STUDY OF DOPAMINE CONTROL IN THE RAT STRIATUM

The control of dopamine release by negative feedback via dopaminergic autoreceptors has been well established. Using previously derived math ematical equations, we have incorporated this feedback component into a mass-action binding model in which the rate of ligand release is a f unction of the quantity that is bound. A consequence of this model is that competitive antagonists augment release, whereas competing agonis ts reduce such release. In order to obtain values of the parameters ne eded in the feedback equations, in vivo microdialysis was used to deli ver drugs locally to the rat striatum and to monitor the resulting cha nges in extracellular dopamine levels. The dopamine agonists apomorphi ne and quinpirole and the antagonists haloperidol and sulpiride were i ndividually infused into the rat striatum via the microdialysis probe, and the effect of each on extracellular dopamine, 3,4-dihydroxyphenyl acetic acid and homovanillic levels was recorded. The data obtained fr om the microdialysis experiments were used to construct dopamine's con trol curve, a new quantitative concept that describes the feedback con trol of the dopaminergic system. Once known, the ligand's control curv e has predictive value that may be useful in the design of efficient d rug tests. Alterations of dopamine's control curve, which may occur wi th aging, drug addiction and pathological states, can now be studied a nd may provide new insights for potential therapeutic strategies.