Progesterone, administered prior to kainic acid, reduces decrements in cognitive performance in the Morris Water Maze.
Summary of "Progesterone, administered prior to kainic acid, reduces decrements in cognitive performance in the Morris Water Maze."
The nature of progesterone (P(4))'s neuroprotective effects is of interest. We investigated effects of P(4) when administered prior to, or following, kainic acid, which produces ictal activity and damage to the hippocampus, to mediate effects on spatial performance. The hypothesis was that P(4), compared to 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 following subcutaneous (s.c.) P(4) administration to ovariectomized rats. Rats administered kainic acid had the highest corticosterone levels immediately following injection. P(4) is 5alpha-reduced to dihydroprogesterone (DHP) and subsequently metabolized to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) by 3alpha-hydroxysteroid dehydrogenase. The regimen of P(4) utilized produced circulating and hippocampal levels of P(4), DHP, and 3alpha,5alpha-THP within a physiological range, which decline at 14 hours post-injection, and were not altered by kainic acid. Experiment 2: The physiological P(4) regimen was administered to rats before, or following, kainic acid-induced seizures, and later effects on water maze performance were compared to 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. (c) 2010 Wiley Periodicals, Inc. Develop Neurobiol, 2010.
Affiliation
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.
Journal Details
This article was published in the following journal.
Name: Developmental neurobiology
ISSN: 1932-846X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20715152
- DOI: http://dx.doi.org/10.1002/dneu.20832
Medical and Biotech [MESH] Definitions
Receptors, Kainic Acid
Cell surface proteins that bind glutamate and directly gate ion channels. Kainic acid receptors were originally discriminated from other glutamate receptors by their affinity for the agonist kainic acid. Activation of kainic acid receptors is generally excitatory to cells. Subtypes have been cloned, and for some the traditional distinction from AMPA receptors may not apply.
Ibotenic Acid
A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist.
Receptors, Progesterone
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.
Kainic Acid
(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.
Progesterone Congeners
Steroidal compounds related to PROGESTERONE, the major mammalian progestational hormone. Progesterone congeners include important progesterone precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with progestational activities.
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