A microdialysis study on striatal dopamine, 5-HT and metabolites in conscious rats after various treatments: evidence for extravesicular release of dopamine.

The effects of death and various treatments that affect the status of nigrostriatal neurones on striatal release of dopamine (DA) and 5-hydroxytryptamine (5-HT) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylethylamine (3-MT), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were studied by in vivo microdialysis. In conscious rats, DA and 5-HT levels were very low compared with their metabolites except 3-MT which was rarely detectable. Upon death by pentobarbitone overdose, there was an immediate surge of the DA level reflecting massive release of the neurotransmitter. This increase was accompanied by a significant increase in 3-MT level but not the other two DA metabolites. Post mortem release of 5-HT was also observed but to a much smaller extent than that of DA. The amounts of amines released appeared to be proportional to the amine stores. When L-dihydroxyphenylalanine (DOPA) was administered to reserpinized rats, the extracellular levels of both DOPAC and HVA increased but not that of DA. However, marked release of DA occurred at death in contrast to reserpinized rats not injected with the precursor. It is evident that exogenous L-DOPA is taken up into the dopaminergic nerve endings and is converted to releasable extravesicular DA, and that this releasable DA is released, at least in part, in accordance with neuronal activities.