GABA (A ) Receptors in the Dorsal Hippocampus are Involved in Sate-dependent Learning Induced by Lithium in Mice

These experiments examined the effects of pre-test intra dorsal hippocampus (intra-CA1) administration of GABA(A) receptor agonist and antagonist, muscimol and bicuculline respectively, on state-dependent learning induced by lithium. Male NMRI mice were trained in a one-trial step-down inhibitory avoidance task, and immediately after training they received IP injections of either saline (10 mL/kg) or lithium (10 mg/kg). The animals were tested for step-down latency, as an index of inhibitory avoidance memory, 24 h after the training. The results showed that lithium (10 mg/kg) induced state-dependent learning. Although the decrease of step down latency due to post-training lithium (10 mg/kg) was not fully reversed by a lower dose of lithium (5 mg/kg) but pre-test intra-CA1 injection of bicuculline (0.25 μg/mouse) increased the effect of the lower dose of lithium. Pre-test intra-CA1 injection of muscimol (0.05 μg/mouse) by itself reversed the decrease of step-down latency induced by post-training lithium (10 mg/kg). Pre-test intra-CA1 injection of muscimol (0.03 and 0.05 μg/mouse) also disrupted state-dependent learning induced by lithium (10 mg/kg). The results suggest that a GABA(A) receptor mechanism in the dorsal hippocampus is involved in state-dependent induced by lithium.