Catecholaminergic involvement in the biphasic effect of ADATN on temperature in mice

A prodrug of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADHTN), 2-amino-6,7-diacetoxy-1,2,3,4-tetrahydronaphthalene (ADATN), was tested for activation of central dopaminergic receptors as measured by colonic temperature in mice. Intraperitoneal injections of ADATN (200 and 800 mumol/kg) produced hypothermia; and intermediate dose (400 mumol/kg) caused hyperthermia followed by hypothermia. A similar biphasic effect occurred with the one dose of ADHTN (800 mumol/kg) tested. Pretreatments with catecholaminergic antagonists were used to characterize the biphasic effect of the intermediate dose of ADATN. The hyperthermic phase depended on the release of endogenous catecholamines which activated alpha- and beta-adrenergic receptors. The hypothermic phase was mediated by a direct activation of dopaminergic receptors. The results are discussed in terms of the pharmacodynamics of a prodrug, the actions of ADHTN, and the known effects of indirect- and direct-acting catecholaminergic agonists on temperature. The involvement of different catecholaminergic systems in the effects of ADATN may limit its usefulness as a dopaminergic prodrug.