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

Abstract

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). GABA B receptor antagonists suppress completely the production of these spike and wave discharges. GABA B 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 GABA B receptor antagonists on this activity. Rats were injected intraperitoneally once per day with saline or a GABA B 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 GABA B receptor antagonists.