Selective storage in vivo of 5,6-ADTN in dopamine-rich areas of the rat brain.
This study investigates the mechanism of the selective storage of the dopamine agonist 2-amino-5,6-dihydroxytetrahydronaphthalene (5,6-ADTN, used as the esterified prodrug) in densely innervated dopaminergic brain structures. The accumulation of 5,6-ADTN in dopamine-rich areas appeared to be non-saturable at the doses studied. In rats with a unilateral 6-OHDA lesion there was a corresponding unilateral decrease in 5,6-ADTN concentrations which suggests that the agonist interacts with dopamine uptake or storage mechanisms. Apart from an initial decreased penetration in the brain, reserpine-induced depletion of dopamine stores did not influence the accumulation of 5,6-ADTN in dopamine-rich areas, which suggests that 5,6-ADTN is taken up in the so-called 'non-reserpine sensitive DA-pool'. Unexpectedly, reserpine pretreatment caused a long-lasting (at least 170 h) decrease of 5,6-ADTN distribution in non-dopaminergic structures. 5,6-ADTN (used as the prodrug) could have a role to play in the elucidation of the significance of the various dopamine pools.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D009281:Naphthalenes / Q000378:metabolism*; D009284:Naphthols / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D009281:Naphthalenes; D009284:Naphthols; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C020196:2-amino-5,6-dihydroxytetralin; D012110:Reserpine; D004298:Dopamine