α2 GABAA RECEPTOR SUB-UNITS IN THE VENTRAL HIPPOCAMPUS AND α5 GABAA RECEPTOR SUB-UNITS IN THE DORSAL HIPPOCAMPUS MEDIATE ANXIETY AND FEAR MEMORY

Temporary neuronal inactivation of the ventral hippocampus with the GABA(A) agonist muscimol suppresses unconditioned fear behavior (anxiety) but inactivation of the dorsal hippocampus does not. On the other hand, inactivating the dorsal hippocampus disrupts fear memory, while inactivating the ventral hippocampus does not. Here we investigate the roles of hippocampal GABAA receptor sub-units in mediating these anxiolytic and amnesic effects of GABAA receptor agonists. We microinfused TPA023 (alpha 2 agonist) or TB-21007 (inverse alpha 5 agonist) into the dorsal or ventral hippocampus prior to testing rats in two animal models of anxiety: the elevated plus-maze and shock-probe burying test. Twenty-four hours later rats were re-tested in the shock-probe chamber with a non-electrified probe to assess their memory of the initial shock-probe experience (i.e., fear memory). We found that TPA023 was anxiolytic in the plus-maze and shock-probe burying tests when microinfused into the ventral hippocampus. However, TPA023 did not affect anxiety-related behavior when infused into the dorsal hippocampus. Conversely, we found that the alpha 5 sub-unit inverse agonist TB-21007 impaired rats' memory of the initial shock-probe experience when infused into the dorsal hippocampus, but not when infused into the ventral hippocampus. This double dissociation suggests that a2 GABAA receptor sub-units in the ventral hippocampus mediate unconditioned fear or anxiety, while a5 GABAA receptor sub-units in the dorsal hippocampus mediate conditioned fear memory. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.