Summary
Male albino rats given a bilateral injection of Baclofen (Lioresal®) (12μg/rat) in the cerebral ventricles showed a behavioral syndrome of activation+ataxia, paddling, tail-pinch hyperresponse and anesthesia. The phase of activation+ataxia was reduced by pretreatment of rats with H 44/68, FLA 63, reserpine, pimozide, phenoxybenzamine, oxypertine or chlorpromazine. The phase of paddling was reduced by pretreatment with FLA 63, reserpine, phenoxybenzamine, oxypertine, chlorpromazine, pimozide+phenoxybenzamine or apomorphine, while administration of clonidine instead of Baclofen caused paddling in non-pretreated rats. The phase of tail-pinch hyperresponse was reduced by reserpine, oxypertine, chlorpromazine or pimozide+phenoxybenzamine, while none of the pretreatments affected Baclofen-induced anesthesia. Drugs which affect mainly tryptaminergic or GABA-ergic functions failed to affect Baclofen-induced behaviors consistently. The findings suggest that dopaminergic and noradrenergic functions play a role in the central effects of Baclofen on behavior of rats.
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Andén, N.-E., Wachtel, H. Biochemical effects of baclofen (β-para-chlorophenyl-GABA) on the dopamine and the noradrenaline in the rat brain. Acta Pharmacol. Toxicol.40, 310–320 (1977).
Biswas, B., Carlsson, A. The effect of intracerebroventricular administered GABA on brain monoamine metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol.299, 41–46 (1977).
Brogden, R. N., Speight, T. M., Avery, G. S. Baclofen (“Lioresal”-CIBA): An independent preliminary report. Curr. Ther.15, 51–61 (1974).
Curtis, D. R., Game, C. J. A., Johnston, G. A. R., McCulloch, R. M. Central effects ofβ-(p-chlorophenyl)-γ-aminobutyric acid. Brain Res.70, 493 to 499 (1974).
Davies, J., Watkins, J. C. The action ofβ-phenyl-GABA derivatives on neurones in the cat cerebral cortex. Brain Res.70, 501–505 (1974).
Ernst, A. M. Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia10, 316–323 (1967).
Fotherby, K. J., Morrish, N. J., Ryall, R. W. Is Lioresal (Baclofen) an antagonist of substance P? Brain Res.113, 210–213 (1976).
Fuxe, K., Hökfelt, T., Ljungdahl, Å., Agnati, L., Johansson, O., Perez de la Mora, M. Evidence for an inhibitory GABA-ergic control of the mesolimbic dopamine neurons: Possibility of improving treatment of schizophrenia by combined treatment with neuroleptics and GABA-ergic drugs. Med. Biol.53, 177–183 (1975).
Gianutsos, G., Moore, K. E. Increase in mouse brain dopamine content by baclofen: Effects of apomorphine and neuroleptics. Psychopharmacology52, 217–221 (1977).
Hudgson, P., Weightman, D. Baclofen in the treatment of spasticity. Br. Med. J.4, 15–17 (1971).
Knutsson, E., Lindblom, U., Martensson, A. Plasma and cerebrospinal fluid levels of baclofen (Lioresal®) at optimal therapeutic responses in spastic paresis. J. Neurol. Sci.23, 473–484 (1974).
Korsgaard, S. Baclofen (Lioresal) in the treatment of neuroleptic-induced tardive dyskinesia. Acta Psychiat. Scand.54, 17–24 (1976).
Nistri, A. Further investigations into the effects of Baclofen (Lioresal) on the isolated spinal cord. Experientia31, 1066–1068 (1975).
Paulson, G. W. Overdose of Lioresal. Neurology26, 1105–1106 (1976).
Randrup, A., Munkvad, I. Behavioural stereotypies induced by pharmacological agents. Pharmakopsychiat.1, 18–26 (1968).
Saito, K., Konishi, S., Otsuka, M. Antagonism between Lioresal and substance P in rat spinal cord. Brain Res.97, 177–180 (1975).
Scheel-Krüger, J., Arnt, J., Magelund, G. Behavioural stimulation induced by muscimol and other GABA agonists injected into the substantia nigra. Neuroscience Lett.4, 351–356 (1977).
Siegel, S. Nonparametric statistics for the behavioural sciences. New York: McGraw-Hill. 1956.
Smith, D. F., Smith, H. B. The effect of prolonged lithium administration on activity, reactivity and endurance in the rat. Psychopharmacologia30, 83–88 (1973).
Waldmeier, P. C., Fehr, B. Effects of baclofen and γ-hydroxybutyrate on rat striatal and mesolimbic 5-HT metabolism. Eur. J. Pharmacol.49, 177–184 (1978).
Waldmeier, P. C., Maitre, L. Effects of baclofen on dopamine metabolism and interaction with neuroleptic effects. Eur. J. Pharmacol.47, 191 to 200 (1978).
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Smith, D.F., Vestergaard, P. The role of monoamines for the central effects of Baclofen on behavior of rats. J. Neural Transmission 46, 215–223 (1979). https://doi.org/10.1007/BF01250787
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DOI: https://doi.org/10.1007/BF01250787