EFFECTS OF GABA(B) 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 a bsence epilepsy rats of Strasboarg (GAERS)). These rats produce period s of behavioural arrest with simultaneous production of cortical spike and wave discharges (SWD). GABA(B) receptor antagonists suppress comp letely the production of these spike and wave discharges. GABA(B) rece ptor ligands have also been reported to affect cognitive performance i n rodents. The present study examined the cognitive performance of GAE RS and the influence of GABA, receptor antagonists on this activity. R ats were injected intraperitoneally once per day with saline or a GABA , receptor antagonist (CGP 36742 (3-amino-propyl-n-butyl-phosphinic ac id) 100 mg/kg; CGP 56433 ([3-{1-(S)-[{3-(cyclohexylmethyl)hydroxy phos phinyl]-2-(S) hydroxy propyl] amino]ethyl]benzoic acid) ([3-(1-(S)-[(3 -(cyclohexylmethyl)hydroxy phosphinyl]-2-(S) hydroxy propyl] amino]eth yl]benzoic acid) 1 mg/kg or CGP 61334 ([3-([3-[(diethoxymethyl)hydroxy phosphinyl]propyl] amino)methyl]-benzoic acid (1 mg/kg). A two-way ac tive avoidance test paradigm with negative reinforcement was used. Unt reated GAERS performed significantly better than non-epileptic rats (P < 0.05) and this enhancement in cognitive performance was sustained i n rats treated with the GABA(B) receptor antagonists.