Glucocorticoids and the hippocampus. Developmental interactions facilitating the expression of behavioral inhibition.
When threatened, the rapid induction of fear and anxiety responses is adaptive. This article summarizes the current knowledge of the neurobiological development of behavioral inhibition, a prominent response occurring in fear and anxiety-provoking situations. In the rat, behavioral inhibition as exemplified by freezing first appears near the end of the second postnatal week. This emergence of freezing coincides with the developmental period marked by the rapid increase in plasma concentrations of glucocorticoids. Studies show that removal of glucocorticoids at this time severely impairs the age-dependent appearance of freezing. This behavioral impairment produced by adrenalectomy, however, is prevented by exogenous glucocorticoid administration. The effectiveness of glucocorticoids in facilitating the development of freezing appears to be caused by its actions in the hippocampus. In particular, glucocorticoids appear to play a vital role in the postnatal cellular development of the hippocampal dentate gyrus. Doses of glucocorticoids shown to reverse the behavioral inhibitory deficits occurring after adrenalectomy are ineffective when hippocampal dentate granule neurons are destroyed by neurotoxins. Notably, site-specific administration of glucocorticoids to the dorsal hippocampus is successful in promoting the occurrence of freezing in the adrenalectomized rat pup. It is hypothesized that glucocorticoids exert their behavioral inhibitory effects by influencing the development of the septohippocampal cholinergic system. Support for this hypothesis is derived from work demonstrating the importance of glucocorticoids on nerve growth factor systems that play a critical role in septohippocampal cholinergic survival.
Takahashi
L K
LK
Department of Psychiatry, University of Wisconsin Medical School, Madison 53719-1179, USA.
D000109:Acetylcholine / Q000502:physiology; D000223:Adaptation, Psychological / Q000502:physiology; D000315:Adrenalectomy; D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D004924:Escape Reaction / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D012688:Septum Pellucidum / Q000502:physiology
D005938:Glucocorticoids; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D000109:Acetylcholine