Effects of the monoamine oxidase A inhibitor moclobemide on hippocampal plasticity in GR-impaired transgenic mice

A reduction in glucocorticoid receptor (GR) function leads to hippocampus-d ependent allocentric spatial learning deficits, altered novelty exploration and disrupted hippocampal long-term potentiation (LTP) in transgenic mice expressing a CR antisense construct. After continuous long-term treatment o f these mice with moclobemide (a reversible inhibitor of monoamine oxidase A). spatial navigation performance but nut accuracy improved during initial acquisition. These changes were associated with a shift of the threshold f or the induction of hippocampal LTP at low stimulation frequencies. Moreove r, novel object exploration increased in both control and transgenic animal s following long-term treatment with moclobemide. These findings open the p ossibility that antidepressants might improve hippocampal function under co nditions of impaired stress hormone regulation, and that these drugs might in part act through this mechanism to attenuate cognitive deficiency in dis orders such as depression. (C) 2001 Published by Elsevier Science Ltd.