Effects of apomorphine on the in vivo release of dopamine and its metabolites, studied by brain dialysis

The effect of apomorphine (0.05-0.5 mg/kg s.c.) on the release of endogenous dopamine and extracellular levels of the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) were examined in vivo by intracerebral dialysis. A dialysis tube was implanted stereotaxically through both caudate nuclei of rats and perfused with Ringer solution at a rate of 2 microliters/min. The amount of dopamine, DOPAC, HVA and 5HIAA in the perfusates was measured by HPLC with electrochemical detection. With the dialysis tube implanted into the striatum of anaesthetized rats it was possible to measure basal levels of dopamine and the metabolites in the perfusates; dopamine, 0.27 +/- 0.05 pmol/20 min (n = 15), DOPAC 43.3 +/- 2.57 pmol/20 min (n = 15), HVA 24.5 +/- 1.89 pmol/20 min (n = 15) and 5HIAA 13.9 +/- 1.77 pmol/20 min (n = 15). The % recoveries of the monoamines through the membrane were estimated to be 12% (dopamine), 21% (DOPAC), 23% (HVA) and 25% (5HIAA). Apomorphine 0.05-0.2 mg/kg decreased the spontaneous release of dopamine by a maximum of approximately 50%. When the dose of apomorphine was raised up to 0.5 mg/kg there was a 100% inhibition of dopamine release. Also, the extracellular levels of the metabolites DOPAC and HVA decreased following apomorphine administration; however there was no consistent change in 5HIAA. These findings indicate that the dopamine autoreceptors decrease dopamine release in vivo by 0-50% while larger decreases probably involve postsynaptic neurons engaging short- as well as long-loop reflexes.