Effect of chronic exposure to methylxanthines on diazepam cerebral binding in female rats and their offsprings.
Caffeine, theophylline or saline were injected daily into female rats during the gestation and lactation periods. Crude synaptosomal membranes were isolated from the brains of offsprings at various stages of development and their ability to specifically bind [3H]diazepam was tested. An other approach consisted of injecting [3H]diazepam into offsprings and cerebral specifically bound diazepam was measured. It was shown that methylxanthines were able to inhibit [3H]diazepam binding by reducing total number of binding sites in the brain of 5- and 15-day-old rats born from treated mothers, with a total recovery of control values at 25 days of age. Moreover, in vivo percentage of cerebral bound diazepam dramatically fell when rats were exposed to methylxanthines in utero and through the mother's milk. Since caffeine and theophylline displace diazepam binding not necessarily in a competitive manner, it is suggested that they could interfere with diazepam as adenosine antagonists.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism*; D005260:Female; D007774:Lactation; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*
D002110:Caffeine; D013806:Theophylline; D003975:Diazepam