Skip to main content
Log in

Dyphenylhydantoin enhancement of diazepam effects on locomotor activity in mice

  • Short Report
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The interaction of diazepam and diphenylhydantoin on locomotor activity and rearing behavior was studied in mice. Pretreatment of mice with diphenylhydantoin (4.0 and 8.0 mg/kg) significantly reversed the stimulatory effects of low doses of diazepam and considerably increased the depressant effects of the benzodiazepine on locomotor activity and rearing. Neither diazepam (up to 4.0 mg/kg), diphenylhydantoin (8.0 mg/kg) alone, nor combined treatment with both drugs affected brain GABA levels and glutamic acid decarboxylase (GAD) activity at any dosage used. The present behavioral and biochemical data suggests that some of the pharmacological effects of diazepam need not be related to GABAergic mechanisms.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  • Braestrup C, Squires RF (1977) Specific benzodiazepine receptors in rat brain characterized by high-affinity 3H-diazepam binding. Proc Natl Acad Sci USA 74:3805–3809

    Google Scholar 

  • Conney AH (1967) Pharmacological implications of microsomal enzyme induction. Pharmacol Rev 19:317–366

    Google Scholar 

  • Czuczwar SJ, Turski L, Kleinrok Z (1981a) Diphenylhydantoin potentiates the protective effect of diazepam against pentylenetetrazol, but not against bicuculline- and isoniazid-induced seizures in mice. Neuropharmacology 20:675–679

    Google Scholar 

  • Czuczwar SJ, Turski L, Turski W, Kleinrok Z (1981b) Effect of combined treatment of phenytoin with diazepam on the susceptibility of mice to electroconvulsions. J Pharm Pharmacol 33:672–673

    Google Scholar 

  • Gallager DW, Mallorga P, Tallman JF (1980) Interaction of diphenylhydantoin and benzodiazepines in the CNS. Brain Res 189:209–220

    Google Scholar 

  • Häfely W, Kulcsar A, Möhler H, Pieri L, Polc P, Schaffner R (1975) Possible involvement of GABA in the central action of benzodiazepines. In: Costa E, Greengard P (eds) Mechanisms of action of benzodiazepines. Raven, New York, pp 131–151

    Google Scholar 

  • Lowe IP, Robins E, Eyerman GS (1958) The fluorometric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem 3:8–18

    Google Scholar 

  • Möhler H, Okada T (1977) Benzodiazepine receptor: Demonstration in the central nervous system. Science 202:849–851

    Google Scholar 

  • Paul SM, Syapin PJ, Paugh BA, Moncada V, Skolnick P (1979) Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam. Nature 281:688–689

    Google Scholar 

  • Sansone M (1980) Influence of benzodiazepine tranquilizers on amphetamine-induced locomotor stimulation in mice. Psychopharmacology 71:63–65

    Google Scholar 

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

    Google Scholar 

  • Sutton I, Simmonds MA (1974) Effects of acute and chronic pentobarbitone on the GABA system in rat brain. Biochem Pharmacol 23:1801–1808

    Google Scholar 

  • Winer BJ (1962) Statistical principles in experimental design. McGraw Hill, New York

    Google Scholar 

  • Woodbury DM (1969) Mechanisms of action of anticonvulsants. In: Jasper H, Ward A, Pope A (eds) Basic mechanisms of the epilepsies. Little Brown, Boston, pp 647–688

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Turski, L., Czuczwar, S.J., Turski, W. et al. Dyphenylhydantoin enhancement of diazepam effects on locomotor activity in mice. Psychopharmacology 76, 198–200 (1982). https://doi.org/10.1007/BF00435278

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00435278

Key words

Navigation