Synthesis and Release of Dopamine in Rat Brain: Comparison Between Substantia Nigra Pars Compacta, Pars Reticulata, and Striatum

Abstract

Dopamine (DA) is synthesized and released not only from the terminals of the nigrostriatal dopaminergic neuronal pathway, but also from the dendrites in the substantia nigra. We have investigated the regulation of the DA turnover, the DA synthesis rate, and the DA release in the substantia nigra pars compacts (SNpc) and pars reticulata (SNpr) in vivo. As a measure of DA turnover, we have assessed the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid. As a measure of the DA synthesis rate, we have determined the 3,4-dihydroxyphenylalanine accumulation after inhibition of aromatic L-amino acid decarboxylase by 3-hydroxybenzylhydrazine. As a measure of DA release, we have investigated the disappearance rate of DA after inhibition of its synthesis by alpha-methyl-p-tyrosine and the 3-methoxytyramine accumulation following monoamine oxidase inhibition by pargyline. Both the DA turnover and the DA synthesis rate increased following treatment with the DA receptor antagonist haloperidol and decreased following treatment with the DA receptor agonist apomorphine in the SNpc and in the SNpr, but the effects of the drugs were less pronounced than in the striatum. gamma-Butyrolactone treatment, which suppresses the firing of the dopaminergic neurons, increased the DA synthesis rate in the striatum (165%), but had no such effect in the SNpc or SNpr. Haloperidol, apomorphine, and gamma-butyrolactone increased, decreased, and abolished, respectively, the DA release in the striatum, but the drugs had no or only slight effects on the alpha-methyl-p-tyrosine-induced DA disappearance and on the pargyline-induced 3-methoxytyramine accumulation in the SNpc or SNpr. Taken together, these results indicate that the DA synthesis rate, but not the DA release, are influenced by DA receptor activity and neuronal firing in the SNpc and SNpr. This is in contrast to the situation in the striatum, where both the DA synthesis rate and the DA release are under such control.

Dopamine release and metabolism in the rat frontal cortex, nucleus accumbens, and striatum: a comparison of acute clozapine and haloperidol

“…The effects of Hal on 3-MT accumulation in the ACC and of CLZ on 3-MT steady-state and accumulation in the ACC and PFC have not previously been described. Further, as demonstrated here for CLZ (compare the effects of CLZ in Tables 2 and 3) and previously reported by others Moleman et al, 1978;Zetterstrom et al, 1985;Nissbrandt et al, 1989), dopamine release and metabolism are clearly dissociable and hence may well represent different neuronal activities.…”

“…However, it has been shown through pharmacological Wood, 1982a,b; and lesion studies Wood, 1982a,b;Wood et al, 1987a,b) that the steady-state concentration and accumulation of 3-MT are reliable indices of dopamine release from neurones (Kehr, 1981;Waldmeier et al, 1981;Wood & Altar, 1988). Further, although the concentrations of DOPAC and HVA or its rate of synthesis have been employed for the assessment of dopamine release and impulse flow (Demarest & Moore, 1979;Roth et al, 1976), these metabolites are generally regarded as indices of dopamine synthesis and dopamine turnover (Westerink, 1985;Nissbrandt et al, 1989). In the discussion that follows changes in 3-MT (both steady-state changes and changes in accumulation) are used to indicate relative changes in dopamine release, whereas changes in DOPAC and HVA are used as indices of dopamine rate of utilization and turnover.…”

Nur77 Gene Knockout Alters Dopamine Neuron Biochemical Activity and Dopamine Turnover

“…Both basal and haloperidol-induced DOPAC levels were higher in Nur77 −/ − relative to wild-type mice; however, the discrepancy between DOPAC and HVA levels (both in basal and haloperidol-challenged conditions) was especially intriguing. Normally, high levels of DOPAC should have generated higher HVA contents (Nissbrandt et al 1989;Zetterström et al 1984), which suggests that the conversion of DOPAC into HVA might be altered in Nur77 −/− mice. This observation is reminiscent of the effect of COMT gene knockout, which induces DOPAC accumulation from the activity of monoamine oxydase, whereas no HVA is produced (Huotari et al 2002).…”

3‐Methoxytyramine Formation Following Monoamine Oxidase Inhibition Is a Poor Index of Dendritic Dopamine Release in the Substantia Nigra

“…Thus, in the striatum DA receptor antagonists, DA reuptake inhibitors and d-amphetamine (d-AMPH) increase, and DA receptor agonists, reserpine, and drugs that inhibit neuronal firing, such as y-hydroxybutyric acid and y-butyrolactone, decrease, the indices of DA release both when assessed with indirect biochemical postmortem methods (Kehr, 1976;Westerink, 1979;Nissbrandt et al, 1989Nissbrandt et al, , 1991Nissbrandt, 1991, 1992) and with microdialysis technique (Imperato and Di Chiara, 1984;Zetterström and Ungerstedt, 1984;Zetterström et al, 1985;Hurd and Ungerstedt, 1989;Heeringa and Abercrombie, 1995;Engberg et al, 1996). However, in the somatodendritic regions there are conflicting results; i.e., when DA release is measured with indirect biochemical postmortem measurements or voltammetry neither of the above mentioned drugs has any profound effect (Westerink, 1979;Magnusson et al, 1987;Nissbrandt et al, 1989Nissbrandt et al, , 1991Nissbrandt, 1991, 1992;Iravani et al, 1996), but all induce clear-cut changes in DA release when measured with microdialysis (Robertson et al, 1991;Santiago and Westerink, 1991;Heeringa and Abercrombie, 1995;Engberg et al, 1996).…”

“…However, in the somatodendritic regions there are conflicting results; i.e., when DA release is measured with indirect biochemical postmortem measurements or voltammetry neither of the above mentioned drugs has any profound effect (Westerink, 1979;Magnusson et al, 1987;Nissbrandt et al, 1989Nissbrandt et al, , 1991Nissbrandt, 1991, 1992;Iravani et al, 1996), but all induce clear-cut changes in DA release when measured with microdialysis (Robertson et al, 1991;Santiago and Westerink, 1991;Heeringa and Abercrombie, 1995;Engberg et al, 1996).…”