Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Oxolinic acid and diazepam: Their reciprocal antagonism in rodents

  • 20 Accesses

  • 14 Citations

Abstract

The stimulant effects of oxolinic acid were investigated in rats and mice. This drug, given orally, consistantly induced, in doses ranging from 16 to 256 mg·kg-1, locomotor stimulation and stereotyped behavior.

These effects were antagonized by pimozide (1 mg·kg-1), α-methyltyrosine (64 mg·kg-1) or reserpine (4 mg·kg-1, 24 h before testing) pretreatment, suggesting a facilitatory role of oxolinic acid on catecholaminergic processes.

Diazepam (4–16 mg·kg-1) reduced the stimulant effects induced by oxolinic acid but not those induced by amphetamine; oxolinic acid (8 mg·kg-1) markedly reduced the antipunishment effect elicited in rats by diazepam (2 mg·kg-1). Since benzodiazepines have been reported to enhance GABA functioning, these data suggest that oxolinic acid may impair GABA transmission. However, neither muscimol (0.5–1 mg·kg-1) or γ-acetylenic-GABA (16–64 mg·kg-1) selectively reduced the stimulant effects elicited by oxolinic acid. Therefore, the possible facilitation exerted by this drug on catecholaminergic systems may not derive from the release of an inhibitory GABAergic control.

This is a preview of subscription content, log in to check access.

References

  1. Arnt, J.: Christensen, A. V., Scheel-Krüger, J.: Benzodiazepines potentiate GABA-dopamine stereotyped dependent gnawing in mice. J. Pharm. Pharmacol. 31, 56–58 (1979)

  2. Billingsley, M. L., Kubena, A. K.: Effects of naloxone and picrotoxin on the sedative and anticonflict effects of benzodiazepines. Life Sci. 22, 897–906 (1978)

  3. Chermat, R., Kloczko, J., Simon, P.: Oxolinic acid, a new psychoanaleptic? Communication presented at the XIth Congress of the Collegium Internationale Neuropsychopharmacologicum, Vienna 1978

  4. Chermat, R., Kloczko, J., Warot, D., Simon, P.: Effects psychoana-leptiques de l'acide oxolinique. J. Pharmacol. (Paris) 10, 145–157 (1979)

  5. Curtis, D. R., Lodge, D.: Pentobarbitone enhancement of the inhibitory action of GABA. Nature 270, 543–544 (1977)

  6. Haefely, W.: Behavioral and neuropharmacological aspects of drugs used in anxiety and related states. In: Psychopharmacology: A generation of progress, M. A. Lipton, A. Dimascio, K. F. Killam, eds., pp. 1359–1374 New York: Raven Press 1978

  7. Lhermitte, F., Signoret, J.-L., Agid, Y., Laffont, F., Jouvent, L. R.: Traitement d'un état hallucinatoire avec hypersomnie diurne par l'acide oxolinique. Nouv. Presse Med. 43, 3936 (1978)

  8. McMillen, B. A., Shore, P. A.: Amfonelic acid, a non-amphetamine stimulant, has marked effects on brain dopamine metabolism but not noradrenaline metabolism: Association with differences in neuronal storage systems. J. Pharm. Pharmacol. 30, 464–466 (1978)

  9. Menon, M. K., Clark, W. G.: GABA-ergic drugs block locomotor stimulant effects of 1,3-dimethyl-5-aminoadamantane (D 145). Neuropharmacology 18, 223–225 (1979)

  10. Möhler, H., Okada, T.: GABA receptor binding with 3H(+)bicuculline methiodide in rat CNS. Nature 267, 65–67 (1977)

  11. Racagni, G., Bruno, F., Cattabeni, F., Maggi, A., Di Guillio, A. M., Parenti, M., Gropetti, A.: Functional interaction between substantia nigra and striatum: GABA and dopamine interrelation. Brain Res. 134, 353–358 (1977)

  12. Schechter, P. J., Tranier, Y., Jung, M. J., Sjoerdsma, A.: Antiseizure activity of γ-acetylenic-γ-aminobutyric acid: A catalytic irrever-sible inhibitor of γ-aminobutyric acid transaminase. J. Pharmacol. Exp. Ther. 201, 606–612 (1977)

  13. Scheel-Krüger, J., Christensen, A. V., Arnt, J.: Muscimol differentially facilitates stereotypy but antagonizes motility, induced by dopaminergic drugs: A complex GABA-dopamine interaction. Life Sci. 22, 75–84 (1978)

  14. Simon, P., Chermat, R.: Recherche d'une interaction avec les stéréotypies provoquées par l'amphètamine chez le Rat. J. Pharmacol. (Paris) 3, 235–238 (1972)

  15. Simon, P., Chermat, R.: Insomnie imputable à l'acide oxolinique. Nouv. Presse Med. 6, 3754 (1977)

  16. Soubrié, P., Simon, P., Boissier, J. R.: Effects du diazépam sur six modèles d'hyperactivité chez la Souris. Psychopharmacologia (Berl.) 45, 197–201 (1975)

  17. Soubrié, P., Simon, P., Boissier, J. R.: Antagonism of diazepam against central anticholinergic drug-induced hyperactivity in mice: Involvement of a GABA mechanism. Neuropharmacology 15, 773–776 (1976)

  18. Soubrié, P., Thiébot, M. H., Simon, P. Enhanced suppressive effects of aversive event induced in rats by picrotoxin: Possibility of a GABA control on behavioral inhibition. Pharmac. Biochem. Behav. 10, 463–469 (1979)

  19. Stein, L., Belluzi, J. D., Wise, D.: Benzodiazepines: Behavioral and neurochemical mechanism. Am. J. Psychiatry 134, 665–669 (1977)

  20. Thiébot, M. H., Soubrié, P.: Amphetamine-induced circling behavior in rats: Effects of unilateral microinjections of GABA and GABA-related drugs into substantia nigra. Brain Res. 167, 307–322 (1979)

  21. Valli, M., Bouyard, P.: Certains antiseptiques urinaires ont-ils une action psychoanaleptique? Nouv. Presse Méd. 7, 1114 (1978)

  22. Young, A. B., Enna, S. J., Zukin, S. R., Snyder, S. H.: Synaptic GABA receptor in mammalian CNS. In: GABA in nervous system function, E. Roberts, T. N. Chase, D. B. Tower, eds., pp. 305–317. New York: Raven Press 1976

Download references

Author information

Correspondence to Pierre Simon.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Thiébot, M., Kloczko, J., Chermat, R. et al. Oxolinic acid and diazepam: Their reciprocal antagonism in rodents. Psychopharmacology 67, 91–95 (1980). https://doi.org/10.1007/BF00427601

Download citation

Key words

  • Oxolinic acid
  • Diazepam
  • GABA
  • Stereotyped behavior
  • Locomotor stimulation