The neurosteroid pregnenolone sulfate increases cortical acetylcholine release: a microdialysis study in freely moving rats.
The effects of pregnenolone sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.
Darnaudéry
M
M
Psychobiologie des Comportements Adaptatifs, INSERM U. 259, Université de Bordeaux II, France.
Koehl
M
M
Pallarés
M
M
Le Moal
M
M
Mayo
W
W
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C018370:pregnenolone sulfate; D011284:Pregnenolone; D000109:Acetylcholine