Dopamine- and cholecystokinin-containing neurons of the crossed mesostriatal projection

doi:10.1016/0304-3940(83)90044-7

Neuroscience Letters

Volume 40, Issue 3, 10 October 1983, Pages 233-238

https://doi.org/10.1016/0304-3940(83)90044-7 Get rights and content

Abstract

The projection of the substantia nigra-ventral tegmental area (SN-VTA) to the ipsilateral and contralateral caudate-putamen was studied with double-labeling fluorescence techniques in the albino rat. By combining glyoxylic acid histofluorescence with retrograde fluorescence tracers, we were able to determine that 93% of the minor (1–2%) contralateral mesostriatal pathwayis catecholaminergic. In addition, combined immunofluorescence and retrograde fluorescence tracer studies showed that 50% of the crossed mesostriatal pathway also arises from cholecystokinin-containing neurons. These results provide evidence for crossed catecholamine- and peptide-containing pathways in the mesostriatal system which is part of the ‘prefrontal system’ that links the prefrontal cortex through the caudate-putamen, with the thalamus and tectum of each hemisphere.

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Both antisera showed a high density of nerve endings in the striatum, being most numerous medially, but the nonsulfated CCK-immunoreactivity was weaker than that of sulfated CCK (cf. Figs. 5C and 4C). The mesencephalon is known to harbor dopaminergic cells in the substantia nigra (SN) (A9 group) and ventral tegmental area (VTA) (A10 group) (Dahlström and Fuxe, 1964), and many of these cells co-express CCK (Hökfelt et al., 1980; Fallon et al., 1983; Seroogy et al., 1989). Here the antiserum reacting with sulfated CCK only showed a weak, granular staining in the SN of control rats (Fig. 4E, F).
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Investigators did not observe any double-labeled cells. These results were further confirmed using striatal injections of either propoidium iodide or Granular Blue and demonstrate that SN contralateral projections to the striatum account for 1–2% of the ipsilateral projections [22]. Similar findings were observed in young rats (6 and 30 day old) that had received Nuclear Yellow into one striatum and granular blue in the contralateral striatum, finding that crossed cells approximated 1% of ipsilateral cells with 6-day old rats having slightly more crossed cells than the 30 day old group [3].
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Behavioral and pharmacological evidence has shown a different and opposite role of the neuropeptide cholecystokinin (CCK) on the dopamine (DA) function in the caudal versus rostral part of the nucleus accumbens. Previous reports have speculated that the caudal region of the nucleus accumbens would receive CCKergic innervation from dopaminergic neurons of the mesencephalic ventral tegmental area, whereas the CCKergic input to the rostral accumbens would originate in non-dopaminergic neurons from extra-mesencephalic areas of the brain. In the present study, this issue was addressed using retrograde tracing techniques in conjunction with immunocytochemistry. Retrograde tracers were injected in the three compartments of the accumbens (i.e., rostral pole, core and septal shell). In summary, our results demonstrate that 1) the main CCKergic input of the accumbens originates in the ventral mesencephalon; 2) the rostral pole is equally innervated by CCK neurons projecting from both substantia nigra pars compacta and ventral tegmental area; 3) the primary source of CCK innervation of the accumbal core is the substantia nigra pars compacta; and 4) whereas the CCKergic input to the septal shell originates primarily in the ventral tegmental area. Additionally, our results also showed that most of the CCKergic neurons projecting to any of the accumbal compartments also produce dopamine. These data constitute the first neuroanatomical evidence for the differential effects of CCK on dopamine actions in the different regions of the nucleus accumbens.

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^☆: This work was supported by NIH Grants NS 15321 and NS 16017.

¹: The authors wish to thank N. Sepion for typing the manuscript.

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Dopamine- and cholecystokinin-containing neurons of the crossed mesostriatal projection☆

Abstract

Neuroscience

Neurosci. Lett.

Brain Res.

Brain Res.

Neuropeptides

Brain Res.

A striato-striatal connection in rats

Soc. Neurosci. Abstr.

An autoradiographic examination of corticocortical and subcortical projections of the mediodorsal projection (prefrontal) cortex in the rat

J. comp. Neurol.