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

• Published in: Neuroscience Vol. 119; no. 1; pp. 309 - 318
• Main Authors: Julian, M.D., Martin, A.B., Cuellar, B., Rodriguez De Fonseca, F., Navarro, M., Moratalla, R., Garcia-Segura, L.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2003; Elsevier
• Subjects: Animals; Animals, Inbred Strains; Basal Ganglia - anatomy & histology; Basal Ganglia - metabolism; Biological and medical sciences; Cannabinoid Receptor Modulators; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; dopamine; endocannabinoids; Fundamental and applied biological sciences. Psychology; globus pallidus; Immunohistochemistry - methods; In Situ Hybridization - methods; Male; Rats; Rats, Wistar; Receptors, Cannabinoid; Receptors, Drug - genetics; Receptors, Drug - metabolism; RNA Probes - metabolism; striatum; substantia nigra; Sulfur Isotopes - metabolism; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; tyrosine hydroxylase; Vertebrates: nervous system and sense organs; PBTB; THC; striatum; CB1 receptors; SN; globus pallidus; PBS; substantia nigra; SSC; DAB; CPu; GP; SNc; b.w; EDTA; D1; D2; tyrosine hydroxylase; PB; TH; SNr; endocannabinoids; dopamine; CART; DAB-Ni; ERK; Dopamine; Rat; Rodentia; Central nervous system; Basal ganglion; Catecholamine; Vertebrata; Mammalia; Cannabinoid receptor; Neurotransmitter; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00070-8

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.