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GABA-mediated modification of despair behavior in mice

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Summary

Gamma-aminobutyric acid (GABA) and GABA agonists exhibited biphasic response on forced swimming-induced despair behavior in mice; smaller doses, GABA (100 mg/kg), muscimol (0.05 and 0.1 mg/kg), baclofen (0.5 and 1 mg/kg), sodium valproate (100 mg/kg), piracetam (25 mg/kg), and fengabine (10 and 20 mg/kg) decreasing forced swimming-induced immobility period, while higher doses enhancing the immobility period. GABA, muscimol, and baclofen also reversed reserpine-induced prolongation of the forced swimming-induced immobility. When GABA was administered with antidepressant agents, it potentiated the effect of some classical antidepressants. Bicuculline and picrotoxin, the GABAergic antagonists, by themselves enhanced the forced swimming-induced immobility period, but they had no significant effect on reserpine-induced prolongation of the immobility period. When animals were chronically exposed to forced swimming, there was a gradual increase of the immobility period which was reduced on treatment with GABAergic agents. It is suggested that GABA has a modulatory role in reversing forced swimming-induced despair and also in potentiating the effect of antidepressants.

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References

  • Aley KO, Kulkarni SK (1987) Studies on meperidine-induced catelepsy in mice. Meth Find Exp Clin Pharmacol 9:493–496

    Google Scholar 

  • Baldessarini RJ (1980) Drugs and the treatment of psychiatric disorders. In: Gilman AS, Goodman LS, Gilman A (eds) Pharmacological basis of therapeutics. MacMillan, New York, pp 391–447

    Google Scholar 

  • Barbaccia ML, Ravizza L, Costa E (1986) Maprotiline: an antidepressant with an unusual pharmacological profile. J Pharmacol Exp Ther 236:307–312

    Google Scholar 

  • Biswas B, Carlsson A (1978) Effect of intraperitoneally administered GABA on the locomotor activity of mice. Psychopharmacology 59:91–94

    Google Scholar 

  • Bonanno G, Raiteri M (1987) Coexistence of carriers for dopamine and GABA uptake on a same nerve terminal in the rat brain. Br J Pharmacol 91:237–243

    Google Scholar 

  • Borsini F, Meli A (1988) Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 94:147–160

    Google Scholar 

  • Borsini F, Evangelista S, Meli A (1986) Effect of GABAergic drugs in the behavioral despair test in rats. Eur J Pharmacol 121:265–268

    Google Scholar 

  • Bowery NG (1982) Baclofen: 10 years on TIPS 3:400–403

    Google Scholar 

  • DiChiara G, GL (eds) (1981) GABA and the basal ganglia. Adv Biochem Psychopharmacol. Raven Press, New York, 30:129–163

    Google Scholar 

  • Dunham NW, Miya TS (1957) A note on simple apparatus for detecting neurological deficit in rats and mice. J Am Pharmacist Assoc Sci Ed, vol XLVI, 3, March

    Google Scholar 

  • Garelis E, Young SN, Lal S, Sourkes TL (1974) Monoamine metabolites in lumbar CSF: The question of their origin in relation to clinical studies. Brain Res 79:1–8

    Google Scholar 

  • Gold BL, Bowers MB, Roth RH, Sweeney DW (1980) GABA levels in CSF of patients with psychiatric disorders. Am J Psych 137:362–371

    Google Scholar 

  • Hill DR, Bowery NG, Hudson AL (1984) Inhibition of GABA receptor binding by guanyl nucleotide. J Neurochem 42:652–657

    Google Scholar 

  • Korf J, Venema K (1983) Desmethylimipramine enhances the release of endogenous GABA and other neurotransmitter amino acids from the rat thalamus. J Neurochem 40:946–950

    Google Scholar 

  • Kulkarni SK, Mehta AK (1985) Purine nucleoside-mediated immobility in mice: Reversal by antidepressants. Psychopharmacology 85:460–463

    Google Scholar 

  • Kunchandy J, Kulkarni SK (1986) Reversal by α-agonists of diazepam withdrawal hyperactivity in rats. Psychopharmacology 90:198–202

    Google Scholar 

  • Lloyd KG, Morselli PL, Depoortere H, Fourmer 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 18:957–966

    Google Scholar 

  • Lloyd KG, Thuret F, Pilc A (1985) Upregulation of GABAB binding sites in rat frontal cortex: A common action of repeated administration of different classes of antidepressants and electroshock. J Pharmacol Exp Ther 235:191–199

    Google Scholar 

  • Malinge M, Bourin M, Colombel MC, Larousse C (1988) Additive effects of clonidine and antidepressant drugs in the mouse forced-swimming test. Psychopharmacology 96:104–109

    Google Scholar 

  • Nagatani T, Sugihara T, Kodaira R (1984) The effect of diazepam and of agents which change GABAergic functions in immobility in mice. Eur J Pharmacol 97:271–275

    Google Scholar 

  • Parale MP, Kulkarni SK (1986) Clonidine-induced behavioral despair in mice: Reversal by antidepressants. Psychopharmacology 89:171–174

    Google Scholar 

  • Parale MP, Chakravarti S, Kulkarni SK (1987) Evidence of β-adrenergic involvement in forced swimming-induced behavioral despair of mice. Meth Find Exp Clin Pharmacol 9:35–38

    Google Scholar 

  • Pericic D, Manev H, Lakic N (1985) Sex differences in the response of rats to drugs affecting GABAergic transmission. Life Sci 36:541–547

    Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    Google Scholar 

  • Porsolt RD, Berlin A, Blavet N, Deniel M, Jalfre M (1979) Immobility induced by forced swimming in rats: Effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 57:201–210

    Google Scholar 

  • Post RM, Gordon EK, Goodwin FK, Bunney WE Jr (1973) Central norepinephrine in affective illness: MHPG in the cerebrospinal fluid. Science 179:1002–1003

    Google Scholar 

  • Pycock CJ, Horton RW (1976) Possible GABA mediated control of dopamine dependent behavioral effects from the nucleus accumbens of the rat. Psychopharmacology 49:173–198

    Google Scholar 

  • Sanger DJ, Joly D, Depoortere H, Zivkovic B, Lloyd KG (1986) Behavioral profile of progabide in test for anxiolytic and antidepressant drugs. In: Bartholini G, Lloyd KG, Morselli PL (eds) GABA and mood disorders. Raven Press, New York, pp 77–84

    Google Scholar 

  • Schildkraut JJ (1975) The catecholamine hypothesis of affective disorders. A review of supporting evidence. Am J Psych 122:509–522

    Google Scholar 

  • Shukla VK, Garg SK, Mathur VS, Kulkarni SK (1985) GABAergic dopaminergic and cholinergic interaction in perphenazine-induced catatonia in rats. Arch Int Pharmacodyn Ther 278:236–248

    Google Scholar 

  • Suzdak PD, Gianutsos G (1985) Parallel changes in GABAergic and noradrenergic receptor sensitivity following chronic administration of antidepressant and GABAergic drugs: A possible role for GABA in affective disorders. Neuropharmacology 24:217–222

    Google Scholar 

  • Teruel AF, Boix F, Escorihuela RM, Yanez P, Toberia A (1988) Sodium valproate reduces immobility in the behavioral despair test in rats. Eur J Pharmacol 152:1–7

    Google Scholar 

  • Weiss E, Brunner H, Clerc G, Guibert M, Orofiamma B, Paget R, Robert G, Thillez D, Musch B (1986) Multicenter double-blind study of progabide in depressed patients. In: Bartholini G, Lloyd KG (eds) GABA and mood disorders. Raven Press, New York, pp 182–188

    Google Scholar 

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Alev, K.O., Kulkarni, S.K. GABA-mediated modification of despair behavior in mice. Naunyn-Schmiedeberg's Arch Pharmacol 339, 306–311 (1989). https://doi.org/10.1007/BF00173583

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