Nature 268, 652 - 654 (18 August 1977); doi:10.1038/268652a0

Dopamine selectively increases ³H-GABA release from slices of rat substantia nigra in vitro

J.-C. REUBI^*, L. L. IVERSEN & T. M. JESSELL^†

MRC Neurochemical Pharmacology Unit, Department of Pharmacology, Medical School, Hills Road, Cambridge, UK
^*Permanent address: Brain Research Institute, University of Zurich, Zurich Switzerland.
^†To whom correspondence should be addressed.

THE firing rate of the dopaminergic neurones in the substantia nigra (s. nigra) of mammalian brain is controlled largely by descending striatonigral neurones. But new evidence suggests that the activity of nigral neurones may also be modulated by local circuits within the s. nigra, involving a local dendritic release of dopamine². The demonstration that dopamine is present in³, and released⁴⁻⁶ from, the dendrites of nigral neurones both in vitro and in vivo supports this concept. The precise site of action of dopamine in the s. nigra is not known, but a dopamine-sensitive adenylate cyclase has been described in this brain region⁷, apparently located presynaptically on the terminals of striatonigral afferents⁸⁻¹⁰ containing either -aminobutyric acid (GABA) or substance p^11,12. To determine whether presynaptic dopamine receptors in s. nigra are associated with substance P or GABA-containing axon terminals, we have investigated the effects of dopamine on the release of substance P and GABA from superfused slices of rat s. nigra in vitro. Our results show that dopamine stimulates selectively the release of GABA from nerve terminals in s. nigra.

References

1.	Carlsson, A. & Lindqvist, M. Acta Pharmac. tox. 20, 140–144 (1963).
2.	Groves, P. M., Wilson, C. J., Young, S. J. & Rebec, G. V. Science 190, 522–529 (1975).
3.	Björklund, A. & Lindvall, O. Brain Res. 83, 531–537 (1975).
4.	Geffen, L. B., Jessell, T. M., Cuello, A. C. & Iversen, L. L. Nature 260, 258–260 (1976).
5.	Korf, J., Zieleman, M. & Westerlink, B. H. C. Nature 260, 257–258 (1976).
6.	Nieoullon, A., Cheramy, A. & Glowinski, J. Nature 266, 375–377 (1977).
7.	Cuello, A. C. & Iversen, L. L. International Symposium on Interactions among Putative Neurotransmitters in the Brain (eds Garattini, S., Pujol, J. F. & Samanin, R.) (Raven, New York, in the press).
8.	Premont, J., Thierry, A. M., Tassin, J. P., Glowinski, J., Blanc, G. & Bockaert, J. FEBS Lett. 68, 99–104 (1976).
9.	Gale, K., Guidotti, A. & Costa, E. Science 195, 503–505 (1977).
10.	Phillipson, O. T., Emson, P. C., Horn, A. S. & Jessell, T. M. Brain Res. (in the press).
11.	Dray, A. & Straughan, D. W. J. Pharm. Pharmac. 28, 400–405 (1976).
12.	Kanazawa, I., Emson, P. C. & Cuello, A. C. Brain Res. 119, 447–453 (1977).
13.	Iversen, L. L. & Johnston, G. A. R. J. Neurochem. 18, 1939–1950 (1971).
14.	Jessell, T. M., Iversen, L. L. & Kanazawa, I. Nature 264, 81–83 (1976).
15.	Okada, Y. & Hassler, R. Brain Res. 49, 214–217 (1973).
16.	Clement-Cormier, Y. C., Kebabian, J. W., Petzold, G. L. & Greengard, P. Proc. Natl. Acad. Sci U.S.A. 71, 1113–1117 (1974).
17.	Miller, R. J., Horn, A. S. & Iversen, L. L. Molec. Pharmac. 10, 759–766 (1974).
18.	Miller, R. J., Horn, A. S., Iversen, L. L. & Pinder, R. Nature 250, 238–241 (1974).
19.	Paden, C., Wilson, C. J. & Groves, P. M. Life Sci. 19, 1499–1506 (1976).
20.	Aghajanian, G. K. & Bunney, B. S. Naunyn-Schmiedeberg's Arch. Pharmac. 297, 1–7 (1977).
21.	Srinivasan, V., Neal, M. J. & Mitchell, J. F. J. Neurochem. 16, 1235–1244 (1969).