Apomorphine (APO) is receiving renewed interest in its pharmacology not only due to its usefulness in Parkinson's disease but also in the treatment of other neurological and mental diseases (both idiopathic and drug-induced) which normally respond to treatment with dopamine antagonists. Recent reports in the literature and results in our own laboratory suggest very strongly that APO possesses the ability to stimulate presynaptic dopamine receptors and that chronic administration of the drug results in the induction of behavioral supersensitivity for a period of up to 12 days after cessation of that chronic treatment. We propose an in-depth study of possible changes in sensitivity of dopaminergic systems via analysis of time and dose response relationships of APO-induced stereotypic behavior and 3H-spiroperidol binding in mice that have been treated chronically with APO and subsequently subjected to withdrawal from the drug. These analyses will be compared to parallel experiments conducted with another apomorphine N-n-propylnorapomorphine, and an indirect-acting dopamine agonist (dextroamphetamine) and a dopamine antagonist (spiroperidol). We will also attempt to study the effects of long-term APO administration on the rate of dopamine turnover. Establishment of an """"""""agonist-induced supersensitivity of dopamine-mediated behavior"""""""" could have clinical implications in the treatment of neurological and mental diseases with dopamine agonists or antagonists.
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