Effects of GABAA Receptors in Dorsal Hippocampus on Memory Retention of Cholestatic Rats

The molecular mechanisms that result in cognitive deficits following cholestasis are mainly unknown. As there are many GABAA receptors in the hippocampus CA1 region and the crucial role for GABA in modulating memory, we evaluated the effects of GABAA receptor agents in the CA1 of cholestatic rats on memory retention. The interaction between GABAergic and opioidergic systems in the CA1 on memory was also investigated. The effects of administration of GABAA receptor agonist and antagonist, muscimol (60, 120 and 240 ng/ side) and bicuculline (100, 200 and 400 ng/ side), into CA1 on memory retention were studies using passive avoidance learning (PAL) task in bile duct ligated (BDL) rats. Naloxone (250 ng/ side), the mu-opioid receptor antagonist, was also co-administered alone or with bicuculline (400 ng/ side) to indicate the interaction between opioidergic and GABAergic system. Cholestasis inhibited memory retrieval is shown by the decrease in the step-through latency (STLr). Administration of muscimol or bicuculline alone after training potentiated or attenuated respectively amnesia in BDL rats dose-dependently. Naloxone (250 ng /side) alone increased STLr in BDL-treated rats. Bicuculline (100 ng/side) alone antagonized the amnesic effect of muscimol (120 ng/side). Co-administration of bicuculline and naloxone or muscimol and naloxone caused a significant difference in STLr compared to only naloxone treated rats which show the interaction between two systems on memory retention in cholestssis. Bicuculline (100 ng/side) microinjection alone antagonized the amnesic effect of muscimol (120 ng/side). We indicated the contribution of intra-CA1 GABAA receptors on memory retention in cholestatic rats by the PAL test. Blockade of each GABAA or mu-opioid receptors alone could attenuate the amnesia in BDL rats. Furthermore, blockade of both GABAA or mu-opioid receptors reversed the memory deficit in BDL-treated rats, which shows the interaction between GABAergic and opioidergic systems on memory retention in this test.