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: H Kubová, P Mareš
• Journal: Physiological research (Physiol Res) Vol. 61 Issue 3 Pg. 319-23 ( 2012) ISSN: 1802-9973 [Electronic] Czech Republic
• PMID: 22816377 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Carrier Proteins
• Pyrrolidines
• Quinolizines
• Receptors, GABA-A
• Ro 19-8022
• Tspo protein, rat
• Pentylenetetrazole

Topics

• Age Factors
• Animals
• Anticonvulsants (administration & dosage, toxicity)
• Brain (drug effects, metabolism, physiopathology)
• Carrier Proteins (drug effects, metabolism)
• Disease Models, Animal
• Drug Administration Schedule
• Drug Partial Agonism
• Male
• Pentylenetetrazole
• Pyrrolidines (administration & dosage, toxicity)
• Quinolizines (administration & dosage, toxicity)
• Rats
• Rats, Wistar
• Receptors, GABA-A (drug effects, metabolism)
• Seizures (chemically induced, metabolism, physiopathology, prevention & control)
• Substance Withdrawal Syndrome (etiology, metabolism, physiopathology)
• Time Factors