Summary
Intracerebroventricular administration of muscimol, a potent GABA-receptor agonist, counteracted the antinociceptive effect of morphine or β-endorphin in rats as measured by the “tail flick” method. Muscimol's activity was reversed by bicuculline. Isoguvacine, another GABA agonist, as well as nipecotic acid and guvacine, two inhibitors of neuronal and glial uptake of GABA, also antagonized morphine's antinociceptive effect. A role of the central GABA-ergic system in mediating opiate antinociception is proposed.
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References
Altaffer FB, De Balbian Werster F, Hall S, Long CJ, D'Encarnacao P (1970) A simple and inexpensive cannula technique for chemical stimulation of the brain. Physiol Behav 5: 119–121
Baraldi M, Grandison L, Guidotti A (1979) Distribution and metabolism of muscimol in the brain and other tissues of the rat. Neuropharmacology 18:57–62
Belin MF, Aguera M, Tappaz M, McRae-Degueurce A, Bobillier P, Pujol JF (1979) GABA accumulating neurons in the nucleus raphe dorsalis and periaqueductal gray in the rat: a biochemical and radioautographic study. Brain Res 170:279–297
Biggio G, Della Bella D, Frigeni V, Guidotti A (1977) Potentiation of morphine analgesia by muscimol. Neuropharmacology 16:149–150
Buckett WR (1980) Irreversible inhibitors of GABA transaminase induce antinociceptive effects and potentiate morphine. Neuropharmacology 19:715–722
Christensen AV, Arnt J, Scheel-Krüger J (1978) Muscimol antagonizes morphine hypermotility without potentiation of analgesia. Eur J Pharmacol 48:459–462
Contreras E, Tamayo L, Quijada L (1979) Effects of the irreversible inhibition of GABA transaminase upon some morphine effects. Neuropharmacology 18:309–313
Curtis DR, Duggan AW, Felix D, Johnston GAR (1971) Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Res 32:69–96
D'Amour EF, Smith DL (1941) A method for determinating loss of pain sensation. J Pharmacol Exp Ther 72:74–79
Gottesfeld, Z, Kelly JS, Renaud LP (1972) The in vivo neuropharmacology of aminooxyacetic acid in the cerebral cortex of the cat. Brain Res 42:319–335
Ho IK, Loh HH, Way EL (1976) Pharmacological manipulation of gamma-aminobutyric acid (GABA) in morphine analgesia, tolerance and physical dependence. Life Sci 18:1111–1124
Izumi K, Munekata E, Yamamoto H, Nakanishi T, Barbeau A (1980) Effects of Taurine and γ-aminobutyric acid on akinesia and analgesia induced by d-Ala2-Enkephalinamide in rats. Peptides 1:139–146
Johnston GAR, Krogsgaard-Larsen P, Stephanson A (1975) Betel nut constituents as inhibitors of γ-aminobutyric acid uptake. Nature 258:627–628
Karobath M, Placheta P, Lipptisch M, Krogsgaard-Larsen P (1979) Is stimulation of benzodiazepine receptor binding mediated by a novel GABA receptor? Nature 278:748–749
Kramer CJ (1956) Extension of multiple range test to group means with unequal number of replications. Biometrics 12:307–310
Krogsgaard-Larsen P, Johnston GAR, Lodge D, Curtis DR (1977) A new class of GABA agonist. Nature 268:53–55
Liebman JM, Pastor G (1980) Antinociceptive effects of baclofen and muscimol upon intraventricular administration. Eur J Pharmacol 61:225–230
Maggi A, Enna SJ (1979) Characteristics of muscimol accumulation in mouse brain after systemic administration. Neuropharmacology 18:361–367
Mantegazza P, Tammiso R, Vicentini L, Zambotti F, Zonta N (1979) Muscimol antagonism of morphine analgesia in rats. Br J Pharmacol 67:103–107
Meldrum B (1979) Convulsant drugs, anticonvulsant and GABA-mediated neuronal inhibition. In: Krogsgaard-Larsen P, Scheel-Krüger J, Kofod H (eds) GABA-neurotransmitters. Pharmacochemical, biochemical and pharmacological aspects. Munsgaard, Copenhagen, p 390
Nistico' G, Di Giorgio RM, Rotiroti D, Naccari F, Calatroni A (1979) Effects of intraventricular β-endorphin on GABA system in some areas of chick brain. Res Commun Chem Pathol Pharmacol 26:469–478
Ostrovskaya RU, Bulaev VM (1980) Effect of GABA-ergic agents on the analgesic effect of morphine in rats. Bull Exp Biol Med 88:711–714
Scheel-Krüger A, Arnt J, Magelung G (1977) Behavioural stimulation induced by muscimol and other GABA agonists injected into the substantia nigra. Neurosci Lett 4:351
Schon FE, Kelly JS (1974) The characterization of (3H) GABA uptake into the satellite glial cells of rat sensory ganglia. Brain Res 66:289–300
Yaksh TL, Yeung JC, Rudy TA (1976) Systematic examination in the rat of brain sites sensitive to the direct application of morphine: observation of differential effects within the periaqueductal gray. Brain Res 114:83–104
Yoneda Y, Takashima S, Kuriyama K (1976) Possible involvement of GABA in morphine analgesia. Biochem Pharmacol 25:2669–2670
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This study was supported by C.N.R. grant no. CT 77.01401.04
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Zonta, N., Zambotti, F., Vicentini, L. et al. Effects of some GABA-mimetic drugs on the antinociceptive activity of morphine and β-endorphin in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 231–234 (1981). https://doi.org/10.1007/BF00505654
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DOI: https://doi.org/10.1007/BF00505654