Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-08T10:31:11.976Z Has data issue: false hasContentIssue false
  • English
  • Français

Activity of several GABAergic agents on the behavioral “despair” test in rats

Published online by Cambridge University Press:  28 April 2020

A. Fernandez-Teruel ,
F . Boix ,
R .M . Escorihuela ,
T . Guix  and
A . Tobeña
A. Fernandez-Teruel
Affiliation:
Medical Psychology Unit, Dept. Pharmacology and Psychiatry, Medical School, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain
F . Boix
Affiliation:
Medical Psychology Unit, Dept. Pharmacology and Psychiatry, Medical School, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain
R .M . Escorihuela
Affiliation:
Medical Psychology Unit, Dept. Pharmacology and Psychiatry, Medical School, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain
T . Guix
Affiliation:
Medical Psychology Unit, Dept. Pharmacology and Psychiatry, Medical School, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain
A . Tobeña
Affiliation:
Medical Psychology Unit, Dept. Pharmacology and Psychiatry, Medical School, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain
Get access

Summary

The present study was conducted to investigate whether several GABAergic drugs could affect immobility in the behavioral “despair” test (swimming test). The subacute (3 injections) treatment with the GABA-B agonist baclofen 0.5 mg/kg (BC05) partially antagonised the antiimmobility action of imipramine (IMI), whereas muscimol 0.00125 mg/kg (MU ; GABA-A agonist) did not affect the imipramine effect on immobility. The highest doses of baclofen alone increased immobility time, and no effect of muscimol alone was observed on this measure. Other experiments indicated that different doses of δ-α-aminovaleric acid (a GABA-B antagonist and GABA-A agonist) or progabide (a GABA A/B agonist with clinical antidepressive properties) did not modify immobility time. On the other hand, sodium valproate (VPA), chronically administered, was effective in reducing the time of immobility of rats in the swimming test, at doses which did not alter motor activity in an open field test. Since there is evidence indicating that valproate can be considered as a GABA-mimetic agent, the present data is consistent with other results showing an antidepressant-like activity of agents which enhance GABAergic transmission.

Résumé

Résumé

L’objectif de cette étude fut de rechercher comment plusieurs substances GABAergiques peuvent affecter la réponse d’immobilisation dans le test du désespoir comportemental («behavioral despair», test de la nage). Le traitement subaigu (3 injections) avec baclofen (un GABA-B agoniste), 0,5 mg/kg (BC05) montra une antagonisation partielle de l’action anti-immobilisation de l’imipramine (IMI), tandis que le muscimol 0,00125 mg/kg (MU: un GABA-A agoniste) était inactif sur l’effet «anti-desespoir” de l’imipramine. Les doses supérieures de baclofen augmentèrent le temps d’immobilisation, et le muscimol tout seul n‘eut pas d’action sur cette mesure. D‘autres expériences montrèrent une totale absence d’activité de l’acide δ-α-aminovalérique (un GABA-B antagoniste et GABA-A agoniste), et du progabide (un GABA A/B agoniste avec des propriétés antidépressives en clinique), dans la gamme de doses utilisées. D‘autre part, le sodium valproate (VPA) administré chroniquement fut efficace, montrant une réduction du temps d’immobilisation dans le test du «désespoir», avec des doses qui ne modifient pas l’activité motrice dans un test en «open field». Certains arguments indiquent que le valproate peut être considéré comme une substance GABAergique. Les résultats obtenus sont en accord avec d’autres qui ont démontré pour les substances qui améliorent la transmission GABAergique une activité similaire à celle des antidépresseurs.

Keywords

“behavioral despair” testimmobilityGABAergic agentssodium valproate“open field” activityrattest de “behavioral despair”immobilitésubstances GABAergiquessodium valproateactivité dans le test “open field”rat
Type
Original article
Information
Psychiatry and Psychobiology , Volume 4 , Issue 3 , 1989 , pp. 167 - 173
Copyright
Copyright © European Psychiatric Association 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baldino, F. & Geller, H.M. (1981) Sodium valproate enhancement of γ-aminobutyric acid (GABA) inhibition : electrophysiological evidence for anticonvulsant activity. J. Pharmacol. Exp. Ther. 217, 445–450Google ScholarPubMed
Borsini, F.Evangelista, S. & Meli, A. (1986) Effect of GABA-ergic drugs in the behavioral “despair” test in rats. Eur. J. Pharmacol. 121, 265–268CrossRefGoogle Scholar
Bowery, N.G. & Brown, D.A. (1974) Depolarizing actions of γ-aminobutyric acid and related compounds on rat superior cervical ganglia in vitro. Br. J. Pharmacol. 50, 205–218CrossRefGoogle ScholarPubMed
Broadhurst, P.L. (1960) Experiments in psychogenetics : applications of biometrical genetics to the inheritance of behavior.In: Experiments in Personality (H.J., Eysenck, ed.), Routledge & Kegan Paul, London, vol. 1, pp. 1–102Google Scholar
Drugan, R.C.Ryan, S.Minor, T.R. & Maier, S.F. (1984) Librium prevents the analgesia and shuttlebox escape deficit typically observed following inescapable shock. Pharmacol. Biochem. Behav. 21, 749–754CrossRefGoogle ScholarPubMed
Drugan, R.C.Maier, S.F.Skolnick, P.Paul, S.M. & Crawley, J. (1985) An anxiogenic benzodiazepine receptor ligand induces learned helplessness. Eur. J. Pharmacol. 113, 453–457CrossRefGoogle ScholarPubMed
Evangelista, E.Borsini, F. & Meli, A. (1987) Evidence that muscimol acts in the forced swimming test by activating the rat dopaminergic System Life Sci. 41, 2679–2684CrossRefGoogle ScholarPubMed
Fernández-Teruel, A.Boix, F.Guix, T. & Tobeña, A. (1986) Effects of GABA agonists on behavioral despair and activity measures.Neurosci. Lett. suppl. 26, 280Google Scholar
Fernández-Teruel, A.Longoni, B. & Corda, M.G. (1989) Imipramine and GABA-stimulated chloride ip rat cortex. Biol. Psychiatry 25, 971–974CrossRefGoogle Scholar
Gray, J. A. (1982) The Neuropsychology of Anxiety. An Enquiry into the Functions of the Septo-Hippocampal System. Oxford University Press, New YorkCrossRefGoogle Scholar
Hammond, E.J.Wilder, B.J. & Bruni, J. (1981) Central actions of valproic acid in man and in experimental models of epilepsia. Life Sci. 29, 2561–2574CrossRefGoogle Scholar
Lloyd, K.G.Morselli, H.Depoortere, H.Fournier, V.Zivkovic, B.Scatton, B.Broekkamp, C.Worms, P. & Bartholini, G. (1983) The potential use of GABA agonists in psychiatric disorders: evidence from studies with progabide in animal models and clinical trials. Pharmacol. Biochem. Behav. 18, 957–966CrossRefGoogle ScholarPubMed
Lloyd, K.G.Thuret, F. & Pile, A. (1985) Upregulation of γ-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated administration of different classes of antidepressants and electroshock. J. Pharmacol. Exp. Ther. 235, 191–199Google ScholarPubMed
Lloyd, K.G. & Pichat, P. (1986) GABAergic mechanism of action of antidepressant drugs.In: Biological Psychiatry 1985 (C., ShagassR.C., JosiassenW.H., BridgerK. J., WeissD., Stoff & G.M., Simpson, eds.), Elsevier Science Publishers, New York, pp. 914–916Google Scholar
Morag, M. & Myslobodsky, M. (1982) Benzodiazepine antagonists abolish electrophysiological effects of sodium valproate in the rat. Life Sci. 30, 1671–1677CrossRefGoogle ScholarPubMed
Mush, B. & Garreau, M. (1986) An overview of the antidepressant activity of Fengabine (SL 79.229-00) in open clinical studies.In: Biological Psychiatry 1985 (C., ShagassR.C., JosiassenW.H., BridgerK.J., WeissD., Stoff & G.M., Simpson, eds.), Elsevier Science Publ., New York, pp. 920–922Google Scholar
Nakahiro, M.Saito, K.Yamada, I. & Yoshida, H. (1985) Antagonistic effect of δ-aminovaleric acid on bicuculline-insensitive γ-aminobutyric acid B (GABAB) sites in the rat's brain. Neurosci. Lett. 57, 263–266CrossRefGoogle ScholarPubMed
Olpe, H.R.Steinmann, M.W.Pozza, M.F.Brugger, F. & Schmutz, M. (1988) Valproate enhances GABA-A mediated inhibition of locus coeruleus neurones in vitro. Naunyn-Schmiedebergs Arch. Pharmacol. 338, 655–657CrossRefGoogle ScholarPubMed
Petty, F. & Sherman, A.D. (1981) GABAergic modulation of learned helplessness. Pharmacol. Biochem. Behav. 15, 567–570CrossRefGoogle ScholarPubMed
Poncelet, M.Martin, P.Danti, S.Simon, P. & Soubrié, P. (1987) Noradrenergic rather than GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipramine-like drugs in animals. Pharmacol. Biochem. Behav. 28, 321–326CrossRefGoogle ScholarPubMed
Porsolt, R.D.Anton, G.Blavet, N. & Jalfre, M. (1978) Behavioural despair in rats : a new model sensitive to antidepressant treatment. Eur. J. Pharmacol. 47, 379–391CrossRefGoogle Scholar
Rasmussen, K. J.Schneider, H.H. & Petersen, E.N. (1981) Sodium valproate exerts anti-conflict activity in rats without any concomitant rise in forebrain GABA level. Life Sci. 29, 2163–2170CrossRefGoogle ScholarPubMed
Sanger, D.J.Joly, D.Depoortere, H.Zivkovik, B. & Lloyd, K.G. (1986) Behavioral profile of progabide in tests for anxiolytic and antidepressant drugs. In : GABA and Mood Disorders. Experimental and Clinical Research (G., BartholiniK.G., LloydP.L., Morselli, eds.), Raven Press, New York, pp. 77–84Google Scholar
Suranyi-Cadotte, B.E.Dam, T.V. & Quirion, R. (1985) Antidepressant-anxiolytic interaction : decreased density of benzodiazepine receptors in rat brain following chronic administration of antidepressants. Eur. J. Pharmacol. 106, 673–675CrossRefGoogle Scholar
Suzdak, P.D. & Gianutsos, G, (1985) Parallel changes in the sensitivity of γ-aminobutyric acid and noradrenergic receptors following chronic administration of antidepressant and GABA-ergic drugs. Neuropharmacology 24, 217–222CrossRefGoogle Scholar
Tassin, J.P. (1986) Evolution of the ideas on the mechanisms of action of antidepressants : the concept of receptor heteroregulation. Psychiatr. Psychobiol. 1, 62–72Google Scholar
Ticku, M.K. & Davis, W.C. (1981) Effect of valproic acid on [3H]-diazepam and [3H]-dihydropicrotoxinin binding sites at the benzodiazepine-GABA receptor-ionophore complex. Brain Res. 223, 218–222CrossRefGoogle ScholarPubMed
Vellucci, S.V. & Webster, R.A. (1984) The role of GABA in the anticonflict action of sodium valproate and chlordiazepoxide. Pharmacol. Biochem. Behav. 21, 845–851CrossRefGoogle ScholarPubMed
Weiss, E.Brunner, H.Clerc, G.Guibert, M.Orofiamma, B.Pagot, R.Robert, G.Thilliez, D. & Musch, B. (1986) Multicenter double-bind study of progabide in depressed patients. In: GABA and Mood Disorders. Experimental and Clinical Research (G. Bartholini, K.G., Lloyd & P.L., Morselli, eds.), Raven Press, New York, pp. 127–134Google Scholar
Submit a response

Comments

No Comments have been published for this article.