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The Journal of Neuroscience, May 15, 2003, 23(10):4345-4354

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Selective Hippocampal Lesions Do Not Increase Adrenocortical Activity

Frode A. Tuvnes,¹ Hill-Aina Steffenach,¹ Robert Murison,² May-Britt Moser,¹ and Edvard I. Moser¹

¹Centre for the Biology of Memory, Norwegian University of Science and Technology, N-7489 Trondheim, Norway, and ²Department of Biological and Medical Psychology, University of Bergen, 5009 Bergen, Norway

It has been proposed that the hippocampus exerts a tonic inhibitory influence on the hypothalamic–pituitary–adrenal (HPA) stress axis. This claim rests, in particular, on the upregulation of corticosterone secretion and other measures of HPA activity after nonselective lesions of the hippocampal formation. We measured plasma corticosterone concentrations after selective neurotoxic damage to the hippocampus and the subiculum in rats. Concentrations were estimated during rest in the rat's home cage and at several time points after varying degrees of stress. Lesions of the hippocampus did not increase the concentration of corticosterone relative to control rats in any condition. Temporary inactivation of the hippocampus or the ventral subiculum by infusion of the GABA_A receptor agonist muscimol also failed to induce hypersecretion, although hippocampal infusions did impair spatial memory. These results suggest that the hippocampus is not necessary for tonic inhibition of adrenocortical activity and imply that the HPA axis receives efficient negative feedback inhibition from other brain systems too.

Key words: hippocampus; corticosterone; endocrine; adrenocortical; stress; HPA axis; learning; memory; rat

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Received Dec. 2, 2002; revised Feb. 12, 2003; accepted Feb. 24, 2003.

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