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RATIONALE Aging is associated with reduced secretion of, and down-regulation of receptors for, progesterone (P); yet, P's effects when administered to younger and older animals have not been systematically investigated. Some of P's antianxiety effects may be due to its conversion to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) and its subsequent(More)
The importance of progesterone's (P(4)) metabolism by the 5 alpha-reductase type I enzyme was examined in homozygous and heterozygous 5 alpha-reductase type I knockout mice and their wild-type siblings. P(4) (1.0 mg) or vehicle was administered and effects on motor, anxiety, nociceptive, and depression behavior were observed. After testing, whole-brain(More)
In mammals, the suprachiasmatic nuclei (SCN) regulate the timing of LH surges. Recent evidence suggests that vasoactive intestinal peptide (VIP), an abundantly expressed neuropeptide of the SCN, communicates time of day information from the SCN to GnRH neurons. VIP levels in the SCN decrease with age and may be responsible for alterations in LH surges that(More)
The circadian clock that resides in the suprachiasmatic nucleus (SCN) of the hypothalamus is the major neural pacemaker driving most 24-h rhythms in mammals. Several neurotransmitter peptides are synthesized within this nucleus and communicate rhythmically with other cells in the SCN as well as with cells in other regions of the brain. At the present time,(More)
Of the many people that have epilepsy, only about 70% achieve seizure control with traditional pharmacotherapies. Steroids have long been known to influence ictal activity and may have a therapeutic role. This review summarizes recent investigations that have enhanced knowledge of the effects and mechanisms of gonadal, adrenal, and neuroactive steroids on(More)
Testosterone's (T) anti-seizure effects may be mediated in part by actions of its 5alpha-reduced metabolites. To test this hypothesis, T was administered to knockout mice deficient in the 5alpha-reductase type I enzyme and wildtype controls and their ictal activity following pentylenetetrazole (PTZ; 85 mg/kg i.p.) was compared to mice administered vehicle.(More)
Ketogenic diet (KD) is used to manage intractable epilepsy; however, the mechanisms underlying its therapeutic effects are not known. Steroid hormones, such as progesterone and testosterone, are derived from cholesterol, and are readily 5alpha-reduced to dihydroprogesterone and dihydrotestosterone, which are subsequently converted to(More)
Intrinsic rewarding effects of estradiol (E(2)) may underlie some of the sex differences that emerge postpuberty for the prevalence of drug use and behavioral responses to drugs, but the effects and mechanisms of E(2) for reward have not been well characterized. Conditioned place preference (CPP), as measured by the time spent on the(More)
Testosterone's (T) aggression-enhancing effects may be mediated in part by its 5alpha-reduced, 3-hydroxysteroid dehydrogenized metabolite 5alpha-androstane-3alpha,17beta-diol (3alpha-diol). To test this hypothesis, in Expt. 1 gonadectomized (gdx) C21 mice were administered T, 3alpha-diol, or vehicle and were observed in the resident intruder test of(More)
Basic fibroblast growth factor and interleukin-1 beta are known to regulate the expression of other trophic factors and to stimulate reactive gliosis in vivo. S100 beta is a glial-specific putative neurotrophic factor and has been considered a marker of the reactive status of astrocytes. Therefore, we tested the hypothesis that basic fibroblast growth(More)