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.