Learning and memory in the Morris water maze were differentially affected by diazepam and tiagabine

The Morris water-maze (MWM) is a challenging task for rodents determining acquisition, consolidation, and retrieval of the task. Benzodiazepines, acting at the GABA_A-receptor were known to have amnestic effects. Whether GABA transporter (GAT) inhibition exerts similar effects on learning and memory is a matter of debate in mice. Therefore, performance in the MWM was investigated after treatment with diazepam (dia) a agonist at the GABA_A/BDZ-receptor or tiagabine (tia) a GAT inhibitor in mice (C57/Bl6). The study looked differentially for effects during learning and retrieval of the MWM hidden platform task. Drugs were given in a high (dia 2mg/kg; tia 15mg/kg) and low (dia 1mg/kg; tia 7mg/kg) dose, resulting in five different treatment groups during learning: drug naive controls, acutely diazepam or tiagabine treated mice. For the probe trial (PT) groups were split in complete controls, treatment before PT, on PT only, and on all 5 days. Drugs were injected i.p. 30 min before testing. Mice (n=170) were given four acquisition sessions with four trials each, PT was given at the fifth day. In both high dosage groups treatment impaired motor function This was not the case in both low dose treatment groups. In addition, learning and memory was more severely impaired after high dose treatment. GAT inhibition affected both learning and memory differentially compared to diazepam. Together, these results supported evidence for specific GABA/BDZ related impact on learning and memory.