Summary
The behaviour of cats after unilateral injections of muscimol, picrotoxin and bicuculline into the posterior and lateral parts of the substantia nigra was observed. The antagonism between muscimol and picrotoxin was limited to some effects of the drugs: (1) muscimol-induced sniffing, licking and enhanced locomotor activity was attenuated by picrotoxin in contrast to the muscimol-induced contralateral turning which was even enhanced by picrotoxin; (2) picrotoxin-induced balance disorders as well as characteristic motor disturbances in the hind legs remained unaffected following an additional treatment with muscimol. Furthermore, subcutaneously given apomorphine did not affect the picrotoxin-induced balance and hind leg disorders, although the apomorphine-induced stereotyped behaviour itself was enhanced and suppressed by intranigral administration of muscimol and picrotoxin respectively.
The conclusion is reached that there are at least two distinct populations of GABA receptors within the substantia nigra: one group controlling or being controlled by dopaminergic neurons and one group operating fully independently of the former neurons. The similarities to experiments on rats are stressed. The mechanism underlying the muscimol-resistant picrotoxin-induced effects (balance disorders and motor disturbance of the hind legs) is discussed.
Similar content being viewed by others
References
Andén N-E, Dahlström A, Fuxe K, Larsson K (1966) Functional role of the nigro-neostriatal dopamine neurons. Acta Pharmacol Toxicol 24:263–274
Arbilla S, Kamal L, Langer SZ (1979) Presynaptic GABA auto-receptors on GABAergic nerve endings of the rat substantia nigra. Eur J. Pharmacol 57:211–217
Arnt J, Scheel-Krüger J (1979) GABAergic and glycinergic mechanisms within the substantia nigra: pharmacological specificity of dopamine-independent contralateral turning behaviour and interactions with other neurotransmitters. Psychopharmacology (Berl) 62:267–277
Arnt J, Scheel-Krüger J (1980) Intranigral GABA antagonists produce dopamine-independent biting in rats. Eur J Pharmacol 62:51–60
Arnt J, Scheel-Krüger J, Magelund G, Krogsgaard-Larsen P (1979) Muscimol and related GABA receptor agonists: the potency of GABAergic drugs in vivo determined after intranigral injection. J Pharm Pharmacol 31:306–313
Braestrup C, Nielsen M, Krogsgaard-Larsen P, Falch E (1979) Partial agonists for brain GABA/benzodiazepine receptor complex. Nature 280:331–333
Chéramy A, Nieoullon A, Glowinski J (1977) Stimulation effects of γ-hydroxybutyrate on dopamine release from the caudate nucleus and the substantia nigra of the cat. J Pharmacol Exp Ther 203:283–293
Chéramy A, Nieoullon A, Glowinski J (1978a) Inhibition of dopamine release in the cat caudate nucleus by nigral application of glycine. Eur J Pharmacol 47:141–147
Chéramy A, Nieoullon A, Glowinski J (1978b) GABAergic processes involved in the control of dopamine release from nigrostriatal dopaminergic neurons in the cat. Eur J Pharmacol 48:281–295
Deniau JM, Lackner D, Feger J (1978) Effect of substantia nigra stimulation on identified neurons in the VL-VA thalamic complex: comparison between intact and chronically decorticated cats. Brain Res 145:27–35
Di Chiara G, Morelli M, Porceddu ML, Gessa GL (1978) Evidence that nigral GABA mediates behavioural responses elicited by striatal dopamine receptor stimulation. Life Sci 23:2045–2052
De Montis GM, Olianas MC, Serra G, Tagliamonte A, Scheel-Krüger J (1979) Evidence that a nigral GABAergic-cholinergic balance controls posture. Eur J Pharmacol 53:181–190
Feltz P, De Champlain J (1972) Enhanced sensitivity of caudate neurones to microiontophoretic injections of dopamine in 6-hydroxydopamine treated cats. Brain Res 43:601–605
Fibiger HC, Pudritz RE, McGeer PL, McGeer EG (1972) Axonal transport in nigrostriatal and nigro-thalamic neurons: effects of medial forebrain bundle lesions and 6-hydroxydopamine. J Neurochem 19:1697–1708
Glick SD, Jerussi TP, Fleisher, LN (1977) Turning in circles: the neuropharmacology of rotation. Life Sci 18:889–896
Hassler R (1978) Striatal control of locomotion, intentional actions and of integrating and perceptive activity. J Neurol Sci 36:187–224
Hull CD, Bernardi G, Price DD, Buchwald NA (1973) Intracellular responses of caudate neurons to temporally and spatially combined stimuli. Exp Neurol 38:324–336
Hull CD, Levine MS, Buchwald NA, Heller A, Browning RA (1974) The spontaneous firing pattern of forebrain neurons. I. The effects of dopamine and non-dopamine depleting lesions on caudate unit firing patterns. Brain Res 73:241–262
James TA, Starr MS (1978) The role of GABA in substantia nigra. Nature 275:229–230
Kaakkola S, Kääriäinen I (1980) Circling behavior induced by intranigral injections of GABA and muscimol in rats. Psychopharmacology (Berl) 68:31–36
Kilpatrick IC, Starr MS, FLetcher A, James TA, MacLeod NK (1980) Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies. Exp Brain Res 40:45–54
Leviel V, Chéramy A, Nieoullon A, Glowinski J (1979) Symmetric bilateral changes in dopamine release from the caudate nuclei of the cat induced by unilateral nigral application of glycine and GABA-related compounds. Brain Res 175:259–270
MacLeod NK, James TA, Kilpatrick IC, Starr MS (1980) Evidence for a GABAergic nigrothalamic pathway in the rat. I. Electrophysiological studies. Exp Brain Res 40:55–61
MacNeil D, Gower M, Szymanska I (1978) Response of dopamine neurons in substantia nigra to muscimol. Brain Res 154:401–403
Marsden CD (1979) GABA in relation to extrapyramidal diseases, with particular relevance to animal models. In: Krogsgaard-Larsen P, Scheel-Krüger J, Kofod H (eds) GABA-neurotransmitters. Munksgaard, Copenhagen, p 295
Martin GE, Haubrich DR (1978) Striatal dopamine release and contraversive rotations elicited by intranigrally applied muscimol. Nature 275:230–231
Matsui Y, Kamioka T (1978) Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines. Naunyn-Schmiedeberg's Arch Pharmacol 305:219–225
Mendez JS, Finn BW, Dahl KE (1976) Rotatory behaviour induced by glycine injected into the substantia nigra of the rat. Exp Neurol 50:174–179
Mitchell PR, Marin IL (1978) Is GABA release modulated by presynaptic receptors? Nature (London) 274:904–905
Olianas MC, De Montis GM, Concu A, Tagliamonte A, Di Chiara G (1978a) Intranigral kainic acid: Evidence for nigral nondopaminergic neurons controlling posture and behaviour in a manner opposite to the dopaminergic ones. Eur J Pharmacol 49:223–232
Olianas MC, De Montis GM, Mulas G, Tagliamonte A (1978b) The striatal dopaminergic function is mediated by the inhibition of a nigral, nondopaminergic neuronal system via a strio-nigral GABAergic pathway. Eur J Pharmacol 49:233–241
Olpe H-R, Schellenberg H, Koella WP (1977) Rotational behaviour induced in rats by intranigral application of GABA-related drugs and GABA antagonists. Eur J Pharmacol 45:291–294
Olsen RW (1975) Approaches to study of GABA receptors. In: Roberts E, Chase TN, Tower D (eds) GABA in nervous system function. Raven Press, New York, p 287
Olsen RW, Ban M, Miller T (1976) Studies on the neuropharmacological activity of bicuculline and related compounds. Brain Res 102:283–299
Poitras D, Parent A (1978) Atlas of the distribution of monoamine-containing nerve cell bodies in the brain stem of the cat. J Comp Neurochem 179:699–718
Pycock CJ (1980) Turning behaviour in animals. Neuroscience 5:461–514
Reavill C, Jenner P, Leigh N, Marsden CD (1979) Turning behaviour induced by injection of muscimol or picrotoxin into the substantia nigra demonstrates dual GABA components. Neurosci Lett 12:323–328
Scheel-Krüger J, Arnt J, Magelund G (1977) Behavioural stimulation induced by muscimol and other GABA agonists injected into the substantia nigra. Neurosci Lett 4:351–355
Simmonds MA (1980a) Evidence that bicuculline and picrotoxin act at separate sites to antagonize γ-aminobutyric acid in rat cuneate nucleus. Neuropharmacology 19:39–45
Simmonds MA (1980b) A site for the potentiation of GABA-mediated responses by benzodiazepines. Nature 284:558–560
Snider RS, Niemer WT (1964) A stereotaxic atlas of the cat brain. The University of Chicago Press, Chicago
Tanner T (1978) Circling behaviour in the rat following unilateral injections of p-chlorophenyloalanine and ethanolamine-O-sulphate into the substantia nigra. J Pharm Pharmacol 30:158–161
Tarsy D, Pycock Ch, Meldrum B, Marsden CD (1975) Rotational behaviour induced in rats by intranigral picrotoxin. Brain Res 89:160–165
Ungerstedt U (1971) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand (Suppl) 367:50–67
Usunoff KG, Hassler R, Romansky K, Usunova P, Wagner A (1976) The nigrostriatal projection in the cat. J Neurol Sci 28:265–288
Vincent SR, Hattori T, McGeer EG (1978) The nigrotectal projection: a biochemical and ultrastructural characterization. Brain Res 151:159–164
Walters JR, Lakoski JM (1978) Effect of muscimol on single unit activity of substantia nigra dopamine neurons. Eur J Pharmacol 47:469–471
Waszczak BL, Eng N, Walters JR (1980) Effects of muscimol and picrotoxin on single unit activity of substantia nigra neurons. Brain Res 188:185–197
Wolfarth S, Wand P, Sontag K-H (1979a) The effects of intranigral injections of picrotoxin and carbachol in cats with a lesioned nigrostriatal pathway. Neurosci Lett 11:197–200
Wolfarth S, Coelle E-F, Osborne NN, Sontag K-H, Wand P (1979b) Drug-induced stereotypies and asymmetric behaviour after substantia nigra pars posterior (SNPP) lesions in cats. Brain Res 178:545–554
Yarowsky PJ, Carpenter DO (1978a) Receptors for gamma-aminobutyric acid (GABA) on aplysia neurons. Brain Res 144:75–94
Yarowsky PJ, Carpenter DO (1978b) A comparison of similar ionic responses to γ-aminobutyric acid and acetylcholine. J Neurophysiol 41:531–541
York DH, Faber JE (1977) An electrophysiological study of nigrotectal relationship: a possible role in turning behaviour. Brain Res 130:383–386
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wolfarth, S., Kolasiewicz, W. & Sontag, K.H. The effects of muscimol and picrotoxin injections into the cat Substantia nigra . Naunyn-Schmiedeberg's Arch. Pharmacol. 317, 54–60 (1981). https://doi.org/10.1007/BF00506257
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00506257