TY - JOUR
T1 - Effects of high affinity GABAB receptor antagonists on active avoidance responding in rodents with gamma-hydroxybutyrolactone-induced absense syndrome
AU - Getova, DP
AU - Bowery, Norman
PY - 2001/8/1
Y1 - 2001/8/1
N2 - Rationale: Absence seizures in man are behaviourally manifested as arrest and mild jerks mainly of facial muscles, associated in the electroencephalogram with synchronous spike and wave discharges. Gamma-hydroxybutyrolactone (GHBL) administration is currently used as an experimental model of absence seizures in rats and mice. Objective: The aim of the present study was to examine the effects of three potent gamma -aminobutyric acid (GABA)(B) receptor antagonists CGP55845A, CGP62349 and CGP71982 (0.01 mg/kg) on the development of GHBL-induced absence epilepsy and in learning paradigms of active and passive avoidance tests in GHBL-treated mice and rats. Methods: After 4 weeks of development of the absence syndrome, active and passive avoidance tests with negative reinforcement were performed. In both animal species, the absence syndrome was observed after 3 weeks of treatment in the saline group. Results: The GABA(B) receptor antagonists CGP55845A and CGP62349 appeared to suppress the development of the absence syndrome to a greater degree in mice than in rats. CGP71982 suppressed it later than the other two antagonists (fifth week). In an active avoidance test in GHBL-treated mice, the GABA(B) antagonists had different effects - CGP62349 improved learning and memory retention to a greater extent than CGP55845A, whilst CGP71982 had no influence on it. In a passive avoidance test in GHBL-treated mice, the GABA(B) antagonists also had different effects - CGP71982 improved both learning and memory retrieval, whereas CGP55845A and CGP62349 had no effect. In the active avoidance test in GHBL-treated rats, the GABA(B) antagonist CGP55845A improved learning, whereas the other two, CGP62349 and CGP71982, had no effect. In the passive avoidance test the GHBL-treated rats showed an improvement in short memory retrieval. CGP55845A and CGP71982 improved this further, whilst CGP62349 had no effect. Conclusions: GHBL appeared to influence mice and rats in a different manner rats learned the active avoidance task better than the GHBL-treated mice. The present study confirms previous data that GABA(B) antagonists suppress absence behaviour.
AB - Rationale: Absence seizures in man are behaviourally manifested as arrest and mild jerks mainly of facial muscles, associated in the electroencephalogram with synchronous spike and wave discharges. Gamma-hydroxybutyrolactone (GHBL) administration is currently used as an experimental model of absence seizures in rats and mice. Objective: The aim of the present study was to examine the effects of three potent gamma -aminobutyric acid (GABA)(B) receptor antagonists CGP55845A, CGP62349 and CGP71982 (0.01 mg/kg) on the development of GHBL-induced absence epilepsy and in learning paradigms of active and passive avoidance tests in GHBL-treated mice and rats. Methods: After 4 weeks of development of the absence syndrome, active and passive avoidance tests with negative reinforcement were performed. In both animal species, the absence syndrome was observed after 3 weeks of treatment in the saline group. Results: The GABA(B) receptor antagonists CGP55845A and CGP62349 appeared to suppress the development of the absence syndrome to a greater degree in mice than in rats. CGP71982 suppressed it later than the other two antagonists (fifth week). In an active avoidance test in GHBL-treated mice, the GABA(B) antagonists had different effects - CGP62349 improved learning and memory retention to a greater extent than CGP55845A, whilst CGP71982 had no influence on it. In a passive avoidance test in GHBL-treated mice, the GABA(B) antagonists also had different effects - CGP71982 improved both learning and memory retrieval, whereas CGP55845A and CGP62349 had no effect. In the active avoidance test in GHBL-treated rats, the GABA(B) antagonist CGP55845A improved learning, whereas the other two, CGP62349 and CGP71982, had no effect. In the passive avoidance test the GHBL-treated rats showed an improvement in short memory retrieval. CGP55845A and CGP71982 improved this further, whilst CGP62349 had no effect. Conclusions: GHBL appeared to influence mice and rats in a different manner rats learned the active avoidance task better than the GHBL-treated mice. The present study confirms previous data that GABA(B) antagonists suppress absence behaviour.
KW - active and passive avoidance
KW - GABA(B) receptor antagonist
KW - GHB absence epilepsy model
UR - http://www.scopus.com/inward/record.url?scp=0034891477&partnerID=8YFLogxK
U2 - 10.1007/s002130100766
DO - 10.1007/s002130100766
M3 - Article
C2 - 11512048
SN - 0033-3158
VL - 157
SP - 89
EP - 95
JO - Psychopharmacology
JF - Psychopharmacology
ER -