title: Partial agonist of benzodiazepine receptors Ro 19-8022 elicits withdrawal symptoms after short-term administration in immature rats.
abstract: Repeated administration of partial agonist of benzodiazepine receptors Ro 19-8022 (a derivative of quinolizine class) does not elicit withdrawal in adult rats. Our older data demonstrated that single injection of Ro 19-2088 to immature rats induces increased sensitivity to convulsant action of pentylenetetrazol as a withdrawal phenomenon. To know if repeated administration of the partial agonist has the same effect we injected rats at postnatal days 7 to 11 with an anticonvulsant dose of Ro 19-8022 (0.5 mg/kg i.p.) and tested them 24 h, 48 h and 4 days after the last injection. Repeated administration of Ro 19-8022 resulted also in an increased sensitivity to convulsant action of pentylenetetrazol in immature rats (higher incidence and severity of seizures). This effect was significant 24 h after the last injection but only outlined 48 h after administration. No signs of hypersensitivity were seen at 4-day interval. There is a difference between immature and adult brain in an appearance of withdrawal symptom after administration of the partial agonist of benzodiazepine receptors Ro 19-8022.
authors: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. kubova@biomed.cas.cz
authors: H
authors: H
authors: Kubová
authors: P
authors: P
authors: Mareš
mesh_terms: D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D054333:Drug Partial Agonism; D008297:Male; D010433:Pentylenetetrazole; D011759:Pyrrolidines / Q000008:administration & dosage / Q000633:toxicity*; D011807:Quinolizines / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D002352:Carrier Proteins; D011759:Pyrrolidines; D011807:Quinolizines; D011963:Receptors, GABA-A; C076809:Ro 19-8022; C069997:Tspo protein, rat; D010433:Pentylenetetrazole