Allopregnanolone inhibits learning in the Morris water maze.
The progesterone metabolite allopregnanolone (3alpha-OH-5alpha-pregnane-20-one) inhibits neural functions, enhancing the GABA induced GABA(A) receptor activation. This effect is benzodiazepine like and benzodiazepines are known to impair memory. Acute effects of allopregnanolone on the hippocampus dependent spatial learning in the Morris water maze have not been studied. Adult male Wistar rats where injected (i.v.) with allopregnanolone (2 mg/kg), or vehicle, daily for 11 days. At 8 or 20 min after each injection, studies of place navigation were performed in the Morris water maze. Allopregnanolone concentrations in plasma and in nine different brain areas where analyzed by radioimmunoassay. The latency to find the platform was increased 8 min after the allopregnanolone injection, while normal learning was seen after 20 min. Swim speed did not differ between groups. A higher number of rats were swimming close to the pool wall (thigmotaxis) in the 8 min allopregnanolone group compared to the other groups. Allopregnanolone concentrations in the brain tissue at 8 min were 1.5 to 2.5 times higher then at 20 min after the allopregnanolone injections. After vehicle injections the brain concentrations of allopregnanolone were at control levels. Plasma concentrations of allopregnanolone followed the same pattern as in the brain, with the exception of an increase 8 min after vehicle injections. The natural progesterone metabolite allopregnanolone can inhibit learning in the Morris water maze, an effect not caused by motor impairment. The learning impairment might be due to a combination of changed swimming behavior and difficulties in navigation.
Johansson
Inga Maj
IM
Department of Clinical Science, Obstetrics and Gynecology, UKBF 3B, 2nd floor, Umeå University Hospital, S.E.-901 85, Umeå, Sweden. inga-maj.johansson@obstgyn.umu.se
Birzniece
Vita
V
Lindblad
Charlotte
C
Olsson
Tommy
T
Bäckström
Torbjörn
T
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007859:Learning Disabilities / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D011280:Pregnanolone / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013550:Swimming / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000777:Anesthetics; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone; D003345:Corticosterone