Dopaminergic modulation of hippocampal noradrenaline release. Evidence for alpha 2-antagonistic effects of some dopamine receptor agonists and antagonists

Abstract

3H-Noradrenaline release in the rabbit hippocampus and its possible modulation via presynaptic dopamine receptors was studied. Hippocampal slices were preincubated with 3H-noradrenaline, continuously superfused in the presence of cocaine (30 mumol/l) and subjected to electrical field stimulation. The electrically evoked tritium overflow from the slices was reduced by 0.1 and 1 mumol/l dopamine and apomorphine, but significantly enhanced by 10 mumol/l apomorphine or by 0.1 and 1 mumol/l bromocriptine. If the alpha 2-adrenoceptor antagonist yohimbine (0.1 mumol/l) was present throughout superfusion, the inhibitory effects of dopamine and apomorphine were more pronounced and even 10 mumol/l apomorphine and 1 mumol/l bromocriptine inhibited noradrenaline release. Qualitatively similar observations were made in the presence of another alpha 2-antagonist, idazoxane (0.1 mumol/l). In the presence of the D2-receptor antagonist domperidone (0.1 mumol/l) the inhibitory effects of dopamine were almost abolished, whereas both apomorphine (greater than 1 mumol/l) and bromocriptine (greater than 0.01 mumol/l) greatly facilitated noradrenaline release. The D2-receptor agonist LY 171555 (0.1 and 1 mumol/l) significantly reduced the evoked noradrenaline release whereas the D1-selective agonist SK & F 38393 was ineffective at similar concentrations. The effects of LY 171555 were abolished in the presence of domperidone (0.1 mumol/l) but remained unchanged in the presence of yohimbine or idazoxane (0.1 mumol/l, each). At 1 mumol/l the D2-receptor antagonists domperidone and (-)sulpiride significantly increased the evoked noradrenaline release by about 10%. However, at this concentration, domperidone (but not (-)sulpiride) affected also basal tritium outflow. Bulbocapnine and the preferential D1-receptor antagonists SCH 23390 enhanced the evoked noradrenaline release already at 0.1 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)