Effects of GABAB receptor antagonists on learning and memory retention in a rat model of absence epilepsy

A variety of animal models of absence epilepsy have been described and among these exists a genetically susceptible strain of rat (genetic absence epilepsy rats of Strasbourg (GAERS)). These rats produce periods of behavioural arrest with simultaneous production of cortical spike and wave discharges (SWD). GABAB receptor antagonists suppress completely the production of these spike and wave discharges. GABAB receptor ligands have also been reported to affect cognitive performance in rodents. The present study examined the cognitive performance of GAERS and the influence of GABAB receptor antagonists on this activity. Rats were injected intraperitoneally once per day with saline or a GABAB receptor antagonist (CGP 36742 (3-amino-propyl-n-butyl-phosphinic acid) 100 mg/kg; CGP 56433 ([3-(1-(S)-[(3-(cyclohexylmethyl)hydroxy phosphinyl]-2-(S) hydroxy propyl] amino]ethyl]benzoic acid) ([3-{1-(S)-[{3-(cyclohexylmethyl)hydroxy phosphinyl]-2-(S) hydroxy propyl] amino]ethyl]benzoic acid) 1 mg/kg or CGP 61334 ([3-({[3-[(diethoxymethyl)hydroxy phosphinyl]propyl] amino}methyl]-benzoic acid (1 mg/kg). A two-way active avoidance test paradigm with negative reinforcement was used. Untreated GAERS performed significantly better than non-epileptic rats (P < 0.05) and this enhancement in cognitive performance was sustained in rats treated with the GABAB receptor antagonists.