Influence of GBR 12909 and d-amphetamine on indices of catecholamine synthesis and release in rat adrenal glands

Abstract

Our previous results have shown that dopamine (DA) levels in rat adrenal glands could be increased by DA D 2 receptor agonists and that this effect could be blocked by the DA D 2 antagonists domperidone (supposed to be only peripherally active) and raclopride. The data now presented are aiming to characterize the effects of two indirect DA agonists, GBR 12909 and d-amphetamine, on adrenal DA levels (taken as an index of adrenal catecholamine synthesis rate), and on adrenaline (Ad) levels in the heart (assumed to reflect the Ad release from the adrenal medulla). After various periods of s.c. drug administration the rats were decapitated and tissue catecholamine levels were determined in adrenal glands, hearts and forebrains according to standard techniques by high performance liquid chromatography (HPLC) with electrochemical detection. GBR 12909 (15 and 3 mg/kg), a highly selective DA-uptake inhibitor, induced a pronounced dose dependent increase in adrenal DA and heart Ad, though not until 4 hr after administration; this effect persisted for at least 16hr. However, a statistically significant decrease in forebrain DOPAC was observed already after 30 min. The GBR 12909 effects on adrenal DA and heart Ad were blocked by raclopride, but not by domperidone, suggesting a central site of action. d-Amphetamine, in both doses used (2.5 and 5 mg/kg) induced a statistically significant decrease in forebrain DOPAC between 30 min and 2 hr, and an increase in adrenal DA. Heart Ad was not significantly changed. Domperidone (3 mg/kg, 3 hr) blocked the increasing effect of d-amphetamine (2.5 mg/kg, l hr) on adrenal DA, suggesting a peripheral site of action. The data indicate a complex involvement of dopaminergic mechanisms in adrenomedullary function.