Anticonvulsant and other effects of diazepam grow with time after a single treatment.
The hypothesis was tested that some of the effects in rats of the prototypical benzodiazepine, diazepam, would grow (i.e., sensitize) with the passage of time after acute administration as we had previously observed following stimulants, antidepressants, neuroleptics and other compounds. Our principal findings indicate that: 1) A single pretreatment with 0.5 mg/kg of diazepam significantly enhances the anticonvulsant effect of this same dose administered again two weeks later. 2) One injection of 2.5 mg/kg of diazepam significantly sensitizes the catalepsy and ptosis observed following the administration of haloperidol two weeks but not two hours later. These data provide the first evidence for time-dependent sensitization after benzodiazepines and perhaps by implication, of GABA neurons. They may also suggest that acute stimulation of GABA neurons triggers the progressive development of a long-term, antidopaminergic influence. Finally, they raise the question of whether the progressive anxiolytic influence seen during the first week or so of benzodiazepine therapy depends on the passage of time rather than repeated drug treatment.
Antelman
S M
SM
Department of Psychiatry, Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, PA 15213.
Kocan
D
D
Edwards
D J
DJ
Knopf
S
S
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants; D014150:Antipsychotic Agents; D001763:Blepharoptosis / Q000139:chemically induced; D001923:Brain Chemistry / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D005442:Flumazenil; D003975:Diazepam; D004298:Dopamine; D010433:Pentylenetetrazole