The metabolic rate and vulnerability of dopaminergic neurons, and adenosine dynamics in the cerebral cortex, nucleus accumbens, caudate nucleus, and putamen of the common marmoset

Abstract

The pathophysiology of the striatum and cerebral cortex were studied from the pharmacological aspect. Investigation of the dopamine content in the cerebral cortex revealed that the premotor and motor area showed the highest level (61+/-6.2 ng/g). Intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 10 mg/kg reduced the dopamine content in the caudate nucleus and putamen to 2-3% of the control level in common marmosets, while it fell to 60% in the nucleus accumbens. There was no alteration of the dopamine content in the cerebral cortex. Immunohistochemical staining for tyrosine hydroxylase in the midbrains of MPTP-treated marmosets showed almost complete disappearance of dopaminergic cells from the substantia nigra and good preservation of cells in the ventrotegmental area. Dopaminergic cells projecting to the caudate/putamen, nucleus accumbens, and cerebral cortex showed marked, moderate, and no vulnerability to MPTP, respectively. After systemic administration of MPTP, dopaminergic neurons projecting to the caudate nucleus and putamen were damaged equally. However, the compensatory increase of dopamine turnover was more prominent in the putamen than in the caudate nucleus. Thus, nigroputaminal dopaminergic neurons may have a higher level of activity than neurons in the caudate. The neural connections and functions of the caudate nucleus and putamen have already been differentiated anatomically or physiologically. This compensatory increase of the dopamine turnover rate is another aspect of functional differences between the caudate nucleus and putamen. Investigation of the dopamine content in the head, body, and tail of the caudate nucleus showed no differences in the concentration of dopamine. However, a study of the metabolic rate of dopamine using alpha-methyl-p-tyrosine, a tyrosine hydoxylase inhibitor, showed higher metabolism of dopamine in the head of the caudate nucleus in common marmosets. Thus, dopaminergic neurons projecting to the caudate nucleus may show topographical differences in their firing rates. A microdialysis study indicated an increase in the metabolism of adenosine in the striatum of MPTP-treated animals. Cholinergic neurons are interneurons and are one of the main sources of adenosine in the striatum. Dopaminergic input from the substantia nigra acting on cholinergic neurons was decreased following MPTP treatment. The increase of adenosine metabolism suggested that cholinergic neurons in the striatum receive inhibitory inputs from nigrostriatal dopaminergic neurons.

Coaggregation, Cointernalization, and Codesensitization of Adenosine A2A Receptors and Dopamine D2Receptors

“…Adenosine is therefore expected to increase in the striatal extracellular fluid from patients with Parkinson's disease mainly after chronic intermittent L-DOPA treatment and in agreement with the evidence of increased striatal glutamate drive (28). Hence, striatal extracellular levels of adenosine have been found to increase in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease (29). Thus, the wearing off of the antiparkinsonian action of L-DOPA treatment may in part be caused by the simultaneous chronic activation of A 2A R and D 2 R that, according to the present results, may lead to substantial cointernalization of both receptors.…”

Intracerebral microdialysis of adenosine and adenosine monophosphate – a systematic review and meta‐regression analysis of baseline concentrations

“…() and Nomoto et al . () could not be corrected, and these data were excluded from Table and subsequent analyses. Data from (Masana et al .…”

High frequency stimulation of the subthalamic nucleus evokes striatal dopamine release in a large animal model of human DBS neurosurgery

“…However, the maximal concentration in extracellular dopamine attained by these applied stimulus intensities exhibited a relatively high degree of variance between animals (1–4 μM). The variance observed in intensity evoked dopamine responses between animals are not unexpected given the heterogeneity of dopaminergic innervation of the striatum where the recording electrode was located [28] and the precise location of the stimulating electrode within the STN. In contrast to the stimulation intensity dependency, over a range of stimulation frequencies (60 to 240 Hz) and fixed intensity (3 V), striatal dopamine release exhibited a linear increase up to 120 Hz and thereafter attained a plateau.…”