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http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=12270502&dopt=Abstract
The neurosteroid pregnenolone sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats.
Darnaudery M, Pallares M, Piazza PV, Le Moal M, Mayo W.
Laboratoire Stress perinatal et desadaptations comportementales, Universite de Lille 1, 59655 Villeneuve d'Ascq, France. [email protected]
The effects of an infusion of the neurosteroid pregnenolone sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=12015204&dopt=Abstract
GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid.
Barbaccia ML, Colombo G, Affricano D, Carai MA, Vacca G, Melis S, Purdy RH, Gessa GL.
Department of Neuroscience, University of Rome Tor Vergata, Via Tor Vergata 135, 00133 Rome, Italy. [email protected]
Among the pharmacological actions of gamma-hydroxybutyric acid (GHB), some may involve GABA(A) receptor-mediated mechanisms. GHB, however, fails to directly interact with sites for agonists and modulators on the GABA(A) receptor complex. We hypothesized that, in vivo, GHB may interfere with GABA(A) receptor function by altering the brain concentrations of the neurosteroids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, AP) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, THDOC), positive allosteric modulators of GABA-gated chloride currents. In male Wistar rats, GHB dose-dependently (75-1000 mg/kg, i.p.) increased AP, THDOC and their precursors pregnenolone and progesterone in brain cortex and hippocampus. The increases of AP (4-5 fold) and THDOC (3-4 fold) elicited by 300 mg/kg GHB peaked between 30 and 90 min and abated by 180 min. The selective GABA(B) receptor antagonist SCH 50911 (50 mg/kg, i.p.) prevented the action of GHB, while the GABA(B) receptor agonist baclofen (5-10 mg/kg) mimicked it. NCS-382 (50 mg/kg, i.p.), the purported selective antagonist of the GHB receptor, failed to antagonize GHB, but at 300 mg/kg increased brain cortical neurosteroids to the same extent as 300 mg/kg GHB; coadministration of GHB and NCS-382, however, failed to yield an additive effect. These results strongly suggest that GHB, via a GABA(B) receptor-mediated mechanism, increases the brain concentrations of neurosteroids, whose properties as amplifiers of the GABA-gated chloride conductances may play a role in the GABA(A) receptor-mediated pharmacological actions of GHB.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11514647&dopt=Abstract
Neuroactive steroid levels in patients with generalized anxiety disorder.
Semeniuk T, Jhangri GS, Le Melledo JM.
Department of Psychiatry, University of Alberta Hospital, Edmonton, Alberta, Canada. [email protected]
Serum levels of allopregnanolone, pregnenolone sulfate, and dehydroepiandrosterone sulfate were measured in 8 male patients with generalized anxiety disorder (GAD) and 8 healthy control subjects. Results suggest that patients with GAD have significantly lower levels of pregnenolone sulfate than control subjects.
PMID: 11514647 [PubMed - indexed for MEDLINE]
The neurosteroid pregnenolone sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats.
Darnaudery M, Pallares M, Piazza PV, Le Moal M, Mayo W.
Laboratoire Stress perinatal et desadaptations comportementales, Universite de Lille 1, 59655 Villeneuve d'Ascq, France. [email protected]
The effects of an infusion of the neurosteroid pregnenolone sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=12015204&dopt=Abstract
GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid.
Barbaccia ML, Colombo G, Affricano D, Carai MA, Vacca G, Melis S, Purdy RH, Gessa GL.
Department of Neuroscience, University of Rome Tor Vergata, Via Tor Vergata 135, 00133 Rome, Italy. [email protected]
Among the pharmacological actions of gamma-hydroxybutyric acid (GHB), some may involve GABA(A) receptor-mediated mechanisms. GHB, however, fails to directly interact with sites for agonists and modulators on the GABA(A) receptor complex. We hypothesized that, in vivo, GHB may interfere with GABA(A) receptor function by altering the brain concentrations of the neurosteroids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, AP) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, THDOC), positive allosteric modulators of GABA-gated chloride currents. In male Wistar rats, GHB dose-dependently (75-1000 mg/kg, i.p.) increased AP, THDOC and their precursors pregnenolone and progesterone in brain cortex and hippocampus. The increases of AP (4-5 fold) and THDOC (3-4 fold) elicited by 300 mg/kg GHB peaked between 30 and 90 min and abated by 180 min. The selective GABA(B) receptor antagonist SCH 50911 (50 mg/kg, i.p.) prevented the action of GHB, while the GABA(B) receptor agonist baclofen (5-10 mg/kg) mimicked it. NCS-382 (50 mg/kg, i.p.), the purported selective antagonist of the GHB receptor, failed to antagonize GHB, but at 300 mg/kg increased brain cortical neurosteroids to the same extent as 300 mg/kg GHB; coadministration of GHB and NCS-382, however, failed to yield an additive effect. These results strongly suggest that GHB, via a GABA(B) receptor-mediated mechanism, increases the brain concentrations of neurosteroids, whose properties as amplifiers of the GABA-gated chloride conductances may play a role in the GABA(A) receptor-mediated pharmacological actions of GHB.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11514647&dopt=Abstract
Neuroactive steroid levels in patients with generalized anxiety disorder.
Semeniuk T, Jhangri GS, Le Melledo JM.
Department of Psychiatry, University of Alberta Hospital, Edmonton, Alberta, Canada. [email protected]
Serum levels of allopregnanolone, pregnenolone sulfate, and dehydroepiandrosterone sulfate were measured in 8 male patients with generalized anxiety disorder (GAD) and 8 healthy control subjects. Results suggest that patients with GAD have significantly lower levels of pregnenolone sulfate than control subjects.
PMID: 11514647 [PubMed - indexed for MEDLINE]
