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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)
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)
For decades, the ketogenic diet has been an effective treatment of intractable epilepsy in children. Childhood epilepsy is pharmacoresistant in 25–40 % of patients taking the current prescribed medications. Chronic seizure activity has been linked to deficits in cognitive function and behavioral problems which negatively affect the learning abilities of the(More)
Alterations in two components of the brain's insulin signaling pathway, docosahexaenoic acid (DHA) content and phosphoinositide 3-kinase (PI3K) activity, have been implicated in the insulin resistance that is central to type II diabetes mellitus (DM). A 2- to 3-fold increased risk of developing Alzheimer's disease (AD) in patients with type II DM suggests a(More)
The present study was designed to evaluate the effects of acute inhibition of fatty acid oxidation on plasma levels of beta hydroxybutyrate and latency to PTZ-induced seizures in ad libitum- (AL), calorie-restricted normal rodent chow- (CR), and calorie-restricted ketogenic diet (KD)-fed young rats. Young (day 23) Sprague-Dawley rats were fasted for 8 h and(More)
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