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pregnenolone, learning, randomized controlled trial

Christine E Marx, Jimmy Lee, Mythily Subramaniam, Attilio Rapisarda, Dianne C T Bautista, Edwin Chan, Jason D Kilts, Robert W Buchanan, Eu Pui Wai, Swapna Verma, Kang Sim, Jayaraman Hariram, Rajesh Jacob, Richard S E Keefe, Siow Ann Chong
RATIONALE: Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids...
September 2014: Psychopharmacology
C E Marx, D W Bradford, R M Hamer, J C Naylor, T B Allen, J A Lieberman, J L Strauss, J D Kilts
Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses...
September 15, 2011: Neuroscience
Christine E Marx, Richard S E Keefe, Robert W Buchanan, Robert M Hamer, Jason D Kilts, Daniel W Bradford, Jennifer L Strauss, Jennifer C Naylor, Victoria M Payne, Jeffrey A Lieberman, Adam J Savitz, Linda A Leimone, Lawrence Dunn, Patrizia Porcu, A Leslie Morrow, Lawrence J Shampine
The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. Furthermore, clozapine increases pregnenolone in rodent hippocampus, possibly contributing to its superior efficacy. We therefore investigated adjunctive pregnenolone for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics in a pilot randomized, placebo-controlled, double-blind trial...
July 2009: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
N Ladurelle, B Eychenne, D Denton, J Blair-West, M Schumacher, P Robel, E Baulieu
The effects of prolonged intracerebroventricular (i.c.v.) steroid infusions on memory performances (Y-maze arm discrimination test) and on neurosteroids brain levels were studied in young adult male mice. The Y-maze test consisted of two trials separated by a time interval. In the first trial, one arm of the maze (subsequently called novel arm) was closed, and mice were allowed to visit the two accessible arms. After a short 2-h intertrial interval (ITI), control mice explored preferentially the novel arm, whereas with a longer 6-h ITI, they did not remember the location of the novel arm and performed at random level (33% of time spent in each arm)...
March 10, 2000: Brain Research
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