GABA Mediated Circling from Substantia Nigra

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368 Nature Vol. 287 25 September 1980 middle grade gneisses, respectively, and GABA interneurone. Whether turning injection of picrotoxin or bicuculline into the eclogite-facies rocks themselves have behaviour induced by the intranigral nigra ipsilateral to a 6-hydroxydopamine been retrograded to assemblages that are administration of muscimol is due lesion of the nigro-striatal dopamine compatible with those in the enclosing indirectly to alteration of dopamine pathway, results in reduction, abolition or rocks. (2) Admittedly, there is no certainty release in the striatum is disputed, In fact, reversal of the contraversive rotation 16 that equilibrium has been preserved the effect of intranigral injection of produced by apomorphine . All these between mineral cores. However, mineral GABAergic compounds is critically data point to a primary role of a neuronal cores have relatively uniform composi dependent on the exact site of injection, pathway from caudal nigra independent of tions within each sample, and different an issue which has been neglected in the dopamine, which is responsible for the mineral grains within each sample yield correspondence on this topic. mediation of the circling phenomena. The 6 consistent core temperatures • (3) I clearly The initial observation of Tarsy and his importance of this nigral mechanism is stated that pressure estimates for the colleagues'' that picrotoxin injected into emphasized b the work of Papadopoulos country-rock eclogites at Lien, based on substantia nigra zona compacta caused and Huston11 who showed that spon the jadeite content of omphacite, are contraversive rotation was followed by the taneous circling behaviour induced by a minimum values only. Although many of discovery of Scheel-Kruger et al. 12 that unilateral electrolytic lesion of substantia Kroghs' pressure estimates for eclogites in ipsiversive circling resulted from the nigra was not influenced by the removal of the Basal Gneiss terrane are minimum injection of picrotoxin into a caudal nigral the telencephalon (including striatum and values, as he stipulated, others are true site. Subsequently, James and Starr13 neocortex). Indeed, we have demon 14 estimates, based on the coexistence of (and, independently, ourselves ) demon strated that a hemi-transection rostral to orthopyroxene or phengite with garnet strated that the direction of rotation nigra severing all rostral nigral afferents and omphacite. produced by injection of picrotoxin into and efferents does not attenuate rostral nigra is reversed on injection of this contraversive circling induced by intrani L. G. MEDARIS JR compound into caudal nigra, suggesting gral administration of muscimol (unpub Department of Geology the existence of separate GABA mech lished observations). and Geophysics anisms. We obtained similar findings In conclusion, we support Waddington University of Wisconsin injecting picrotoxin, and also muscimol in in his assertion that the contraversive Madison, Wisconsin 53706 caudal and rostral nigra. circling due to intranigral muscimol The circling produced by the action of administration is not due to striatal events.

I. Krogh, E. J. Nacu re 267, 17-19 (1977). muscimol or picrotoxin at each nigral site There can be little doubt as to the 2. Bryhni , I. , Krogh, E. J. & Griffin, W. L. Neues l b. Miner. can be distinguished on the basis of its importance of a non-dopaminergic nigral Abh. 130, 49-{;8 (1977). on intact striatal dopamine output pathway in the mediation of circ 3. Griffi n, W. L. & Brueckner, H.K. Earrh planer. Sci. Leu. (in dependence the press). mechanisms. Thus, while circling induced ling behaviour. The nature of this pathway 4. C arswell, D. A. & Gibb, F. G. F. Lithos (in the press). by injection of GABA-active compounds remains unknown as does its target site. It 5. Mcdaris, L. G. Nature 283,470--472 (1980). 6. Mcdaris. L. G. Lithos (in the press). into rostral nigra is reduced by 6- does not seem to involve the known pro hydroxydopamine lesions of the nigro jections of the nigra to the superior colli 19 striatal pathway, or by systemically culus 18 or thalamus and we are now administered haloperidol, the same investigating the involvement of nigro GABA mediated circling treatments are ineffective in inhibiting reticular pathways. from substantia nigra circling induced by manipulation of 1 13 14 C. REAVILL GABA mechanisms in caudal nigra • • • N. LEIGH between Waddington1 and These findings support Waddington's THE dialogue P. JENNER 2 of non-dopamine-mediated Martin and Haubrich emphasizes the assertions C. D. MARSDEN complexity of the interaction between contraversive circling being induced by striatal dopamine systems and nigral y• muscimol injected into substantia nigra University Department of Neurology, aminobutyric acid (GABA) mechanisms zona reticulata 1. The exact site used by Institute of Psychiatry and King's College as recently pointed out by Arnt and Martin and Haubrich5 is not clear, but Hospital Medical School, 3 Scheel-Kruger • This is particularly true must have involved caudal nigra as Denmark Hill, London SE5, UK when interpreting behavioural changes in muscimol induced contraversive rotation. I. Waddington, J. L. Nature 283, 696-{;97 (1980). terms of biochemical parameters. The However, the muscimol perfused into 2. Martin, G. E. & Haubrich, D. R. Nature 283,697 (1980). 3. Arnt, J. & Scheel-Kruger, J. Naunyn-Schmiedebergs Arch. effects of manipulating nigral GABA substantia nigra also may have reached Pharmak. 310, 43-51 (1979). mechanisms on striatal dopamine release GABA receptors in rostral nigra to 4. Walters, J . R. & Lakoski, J. M. Eur. I . Pharmac. 47, nigro-striatal 469--4 71 (1 978). are complex. While nigral application of activate the ascending 5. Cheramy, A., Nieoullon, A. & Glowinski, J. I. Pharmac. GABAergic drugs, such as muscimol, pathway so causing increased striatal exp. Ther. 203, 283-293 (1977). increases the firing rate of dopaminergic dopamine release. This would account for 6. Martin, G. E. & Haubrich, D. R. Nature 275, 230-231 (1978). neurones4, and the release of dopamine in the simultaneous occurrence of these 7. Waddington, J. L. Br. J. Pharmac. 60, 263- 264P (1 977). 5 7 the ipsilateral caudate nucleus - , GABA phenomena. 8. Cheramy. A., Nieoullon, A. & Glowinski, J. Eur. 1. Pharmac. 48, 281 - 296 (1978). itself exerts a biphasic action first stimu The argument as to whether or not the 9. Cheramy, A., Nieoullon, A. & Glowinski, J. Life Sci. 20, lating and then inhibiting striatal striataldopamine release caused by 811 - 81 6 (1977). 8 10. Levie!, V., Cheramy, A., Nieoullon, A. & Glowinski, J. dopamine release • Furthermore, the intranigral muscimol is responsible for Brain Res. 175, 35 3-356 (1979). nigral application of picrotoxin stimulates contraversive circling is redundant. The 11. Tarsy, D., Pycock, C., Meldrum, B. & Marsden, C. D. dopamine release in the striatum, an effect circling behaviour initiated by an asym Brain Res. 89, 160-165 (1975). 12 . Scheel-Kruger, J., Arnt, J. & Magelund, G. Neurosci. Lett. which is prevented or reversed by diaze metry of striatal dopamine function is 4, 351-356 (1977). 9 re 229-230 (1978). pam , which itself decreases dopamine clearly mediated by strio-nigral fibres and 13. James, T. A. & Starr, M. S. Natu 275, 10 14 . Reavill, C., Jenner, P., Leigh, N. & Marsden, C. D. release in stria tum (presumably by the substantia nigra. Thus, lesioning of the Neurosci. Letr. 12, 323-328 (1979). facilitation of nigral GABA transmission). descending strio-nigral pathway prevents 15 . Garcia-Munoz, M., Nicolaou, N. M., Tulloch, I. F., Wright, A. K. & Arbuthnot!, G. W. Nature 265,363-365 (1977). Some GABAergic terminals (possibly contraversive circling behaviour induced 16. Di Chiara, G., Porceddu, M. L. , Morelli, M., Mulas, M. L. those projecting to zona compacta) by the administration of apomorphine to & Gessa, G. L Naunyn -Schmiedebergs Arch. Pharmak. therefore seem to inhibit the activity of animals with a unilateral 6-hydroxy 306, 153-159 (1979). 17. Papadopoulos, G. & Huston,}. P. Neurosci. Lerr.13, 63-{;7 nigral dopamine cells, while others dopamine lesion of the nigro-striatal (1979). 15 (possibly those projecting to zona reti pathway • In addition, kainic acid 18. Reavill, C., Lei11h , N., Jenner, P. & Marsden, C. D. Exp/ Brain Res. 37, 309- 316 (1979). culata) may indirectly activate the same induced destruction of neurones in 19. Jenner, P., Leigh, N., Marsden, C. D. & Reavill, C. Br. J. nigral dopamine cells, perhaps via a substantia nigra zona reticulata, or the Pharmac. 67, 432P (1979).