Precipitated abstinence in the diazepam-dependent rat.
Pharmacol Biochem Behav
; 46(3): 683-8, 1993 Nov.
Article
em En
| MEDLINE
| ID: mdl-8278446
Physical dependence was produced in the rat by exposure to continuous release of diazepam from silastic capsule implants (recrystallized diazepam) or by dosing through a gastric fistula. The precipitated abstinence syndrome induced by the IV infusion of flumazenil was characterized by clonic and tonic-clonic seizures, retropulsion, digging, rearing, head, limb and body tremors, twitches and jerks of the body, and ear twitches. This abstinence syndrome differed both qualitatively and quantitatively from the milder syndrome induced in previous experiments by the intragastric administration of flumazenil in the diazepam-dependent gastric fistula rat. Capsule-implanted rats had free plasma and extraneuronal brain levels of diazepam, oxazepam, and nordiazepam in the 10(-3) and 10(-4) mg/ml range, and their brain: plasma ratios were not significantly different from 1. The diazepam capsules had a sustained release of over 28 days. These studies show that the capsule implantation technique is an efficacious way of maintaining plasma levels of diazepam and its metabolites, and producing a high level of physical dependence in the rat.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
/
Transtornos Relacionados ao Uso de Substâncias
/
Diazepam
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Biochem Behav
Ano de publicação:
1993
Tipo de documento:
Article
País de publicação:
Estados Unidos