Abstract
The protective effects of acute and chronic diazepam administration (4 mg/kg) against seizures induced by pentylenetetrazole (PTZ) and picrotoxin were investigated. Considering the incidence of tonic-clonic convulsions, tolerance to the protective effects of diazepam was evident by day 5 if the mice were challenged with PTZ (120 mg/kg), by day 10 if the challenge was picrotoxin (8 mg/kg) and by day 20 if the challenge was PTZ (105 mg/kg). Diazepam retained its protective effects against tonic-clonic convulsions induced by PTZ (90 and 60 mg/kg) for 45 days, but the incidence of myoclonic jerks revealed tolerance after 5 days.
References
Cook L, Sepinwall J (1975) Behavioral analysis of the effects and mechanisms of action of the benzodiazepines. In: Costa E, Greengard, P (eds) Raven, New York, pp 1–27
Cooper SJ, Burnett G, Brown K (1981) Food preference following acute or chronic chlordiazepoxide administration: tolerance to antineophobic action. Psychopharmacology 73:70–74
File SE (1981a) Behavioral pharmacology of benzodiazepines. Paper presented to CINP meeting, Hong-Kong. Prog Neuro-psychopharmacol Biol Psychiatr (in press)
File SE (1981b) Rapid development of tolerance to the sedative effects of lorazepam and triazolam in rats. Psychopharmacology 73:240–245
File SE (1982) The rat corticosterone response: habituation and modification by chlordiazepoxide. Physiol Behav 29:91–95
File SE, Hyde JRG (1978) Can social interaction be used to measure anxiety? Br J Pharmacol 62:19–24
Goldberg ME, Manian AA, Efron DE (1967) A comparative study of certain pharmacologic responses following acute and chronic administrations of chlordiazepoxide. Life Sci 6:481–491
Juhasz L, Dairman W (1977) Effect of subacute diazepam administration in mice on the sunsequent ability of diazepam to protect against metrazol and bicuculline induced seizures. Fed Proc 36:377
Lippa AS, Regan B (1977) Additional studies on the importance of glycine and GABA in mediating the actions of benzodiazepines. Life Sci 21:1779–1784
Stein L, Berger BD (1971) Psychopharmacology of 7-chloro 5-(0-chlorophenyl)-1,3-dihydroxy-2H-1,4-benzodiazepines-2-one (Lorazepam) in squirrel monkey and rat. Arzneim Forsch 21:1073–1078
Vellucci SV, File SE (1979) Chlordiazepoxide loses its anxiolytic action with long-term treatment. Psychopharmacology 62:61–65
Wise CD, Berger BD, Stein L (1972) Benzodiazepines: anxiety-reducing activity by reduction of serotonin turnover in the brain. Science 177:180–183
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File, S.E. Tolerance to the anti-pentylenetetrazole effects of diazepam in the mouse. Psychopharmacology 79, 284–286 (1983). https://doi.org/10.1007/BF00427828
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DOI: https://doi.org/10.1007/BF00427828