Elsevier

Neuroscience

Volume 119, Issue 1, 18 June 2003, Pages 309-318
Neuroscience

Research paper
Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia

https://doi.org/10.1016/S0306-4522(03)00070-8Get rights and content

Abstract

Dopamine and endocannabinoids are neurotransmitters known to play a role in the activity of the basal ganglia motor circuit. While a number of studies have demonstrated functional interactions between type 1 cannabinoid (CB1) receptors and dopaminergic systems, we still lack detailed neuroanatomical evidence to explain their relationship. Single- and double-labeling methods (in situ hybridization and immunohistochemistry) were employed to determine both the expression and localization of CB1 receptors and tyrosine hydroxylase (TH) in the basal ganglia. In the striatum, we found an intense signal for CB1 receptor transcripts but low signal for CB1 receptor protein, whereas in the globus pallidus and substantia nigra we found the opposite; no hybridization signal but intense immunoreactivity. Consequently, CB1 receptors are synthesized in the striatum and mostly transported to its target areas. No co-expression or co-localization of CB1 receptors and TH was found. In the caudate-putamen, globus pallidus and substantia nigra, TH-immunoreactive fibers were interwoven with the CB1 receptor-immunoreactive neuropil and fibers. Our data suggest that the majority of the striatal CB1 receptors are located presynaptically on inhibitory GABAergic terminals, in a position to modulate neurotransmitter release and influence the activity of substantia nigra dopaminergic neurons. In turn, afferent dopaminergic fibers from the substantia nigra innervate CB1 receptor-expressing striatal neurons that are known to also express dopamine receptors. In conclusion, these data provide a neuroanatomical basis to explain functional interactions between endocannabinoid and dopaminergic systems in the basal ganglia.

Section snippets

Animals

This study was carried out on inbred adult (2–3 months old, 250–300 g body weight [b.w.]) male Wistar rats. Rats received food and water ad libitum and were kept in a 12-h light/dark cycle. The maintenance of the animals as well as the experimental procedures followed the guidelines from the European Union (Council Directive 86/609/EEC). All efforts were made to minimize the number of animals used and their suffering.

Tissue preparation for in situ hybridization

Rats were killed by rapid decapitation and their brains were removed and

Results

In the autoradiographic films, we observed high CB1 receptor mRNA expression in the dorsolateral part of the caudate putamen (CPu) at its rostral and middle levels, and in the ventral areas of its pole (Fig. 1A, B). The expression was gradually more intense toward the lateral part of the striatum and less intense in the ventral striatum. In the emulsion-dipped slides, it was evident that the hybridization signal was mainly in the medium-sized striatal neurons. The intensity of the

Discussion

The simultaneous study of the localization of the mRNA and protein for both the CB1 receptor and TH has allowed us to establish the neuroanatomical independence but intimate proximity in the arrangement of the circuitries of the cannabinoid and dopaminergic systems. In agreement with previous studies Mailleux and Vanderhaeghen 1992, Marsicano and Lutz 1999, Hohmann and Herkenham 2000, we have observed high CB1 receptor mRNA expression in the dorsolateral part of the rostral and middle thirds of

Acknowledgments

Plasmids for the CB1 receptor cDNA and TH cDNA were kindly provided by Dr. A. Santos, Universidad Complutense, Madrid, Spain, and Dr. J. Mallet, Hopital de la Pitie Salpetriere, Paris, France, respectively. The CB1-receptor antibody was a present from Dr. A. C. Howlett (North Carolina Central University, Durham, NC, USA). It is greatly appreciated the technical assistance of Concepcion Bailon and Carmen Hernandez for the confocal microscopy images. This work was supported by Plan Nacional sobre

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    1

    R. Moratalla and L. M. Garcia-Segura contributed equally to this study.

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