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Progesterone, administered before kainic acid, prevents decrements in cognitive performance in the Morris Water Maze
Author(s) -
Frye Cheryl A.,
Walf Alicia
Publication year - 2011
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20832
Subject(s) - kainic acid , endocrinology , hippocampal formation , hippocampus , medicine , morris water navigation task , corticosterone , water maze , elevated plus maze , chemistry , hormone , anxiety , glutamate receptor , receptor , psychiatry
The nature of progesterone (P 4 )'s neuroprotective effects is of interest. We investigated effects of P 4 when administered before, or after, kainic acid, which produces ictal activity and damage to the hippocampus, to mediate effects on spatial performance. The hypothesis was that P 4 , compared with vehicle, would reduce decrements in Morris Water Maze performance induced by kainic acid. Experiment 1: We examined the effects of kainic acid on plasma stress hormone, corticosterone, and progestogen (P 4 and its metabolites) levels in plasma and the hippocampus after subcutaneous (s.c.) P 4 administration to ovariectomized rats. Rats administered kainic acid had the highest corticosterone levels immediately following injection. P 4 is 5α‐reduced to dihydroprogesterone (DHP) and subsequently metabolized to 5α‐pregnan‐3α‐ol‐20‐one (3α,5α‐THP) by 3α‐hydroxysteroid dehydrogenase. The regimen of P 4 used produced circulating and hippocampal levels of P 4 , DHP, and 3α,5α‐THP within a physiological range, which declined at 14 hours postinjection and were not altered by kainic acid. Experiment 2: The physiological P 4 regimen was administered to rats before, or after, kainic acid‐induced seizures, and later effects on water maze performance were compared with that of rats administered vehicle. Rats administered kainic acid had significantly poorer performance in the water maze (i.e., increased latencies and distances to the hidden platform) than did rats administered vehicle. Administration of P 4 before, but not after, kainic acid prevented these performance deficits. Thus, these data suggest that a physiological regimen of P 4 can prevent some of the deficits in water maze performance produced by kainic acid. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 142‐152, 2011