Evidence for dopamine release and metabolism beyond the control of nerve impulses and dopamine receptors in rat substantia nigra

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Abstract
In rat substantia nigra a biphasic disappearance curve of dopamine (DA) was seen after tyrosine hydroxylase inhibition by α-methyl-p-tyrosine (α-MT): the initial phase had a fast turnover and a half life of 0ṁ5 h and the later phase had an extremely slow turnover. In contrast to the effects in striatum, neither haloperidol nor apomorphine influenced α-MT-induced DA disappearance in the substantia nigra. Furthermore, inhibition of impulse flow by γ-butyrolactone prevented DA disappearance in striatum but not in the substantia nigra. Measurements of DA and 3-methoxytyramine following treatment with inhibitors of monoamine oxidase (pargyline) and catechol-O-methyl transferase (tropolone) indicated that O-methylation is a more important metabolic pathway in the substantia nigra than in the striatum. The data are interpreted to indicate that the release and metabolism of DA in the substantia nigra are largely beyond the control of nerve impulses and DA receptors. It is suggested that such an arrangement forms an important feature of autoreceptor-mediated feedback control of DA nerve cell activity.