Tolerance development to Morris water maze test impairments induced by acute allopregnanolone
2006 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 139, no 2, 651-659 p.Article in journal (Refereed) Published
The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.
Place, publisher, year, edition, pages
Elsevier Inc. , 2006. Vol. 139, no 2, 651-659 p.
Rat, animal, tolerance, withdrawal, allopregnanolone, morris water maze, learning, memory
Pharmacology and Toxicology Endocrinology and Diabetes Clinical Science Medical and Health Sciences
Research subject Obstetrics and Gynaecology
IdentifiersURN: urn:nbn:se:umu:diva-22548DOI: 10.1016/j.neuroscience.2005.12.031OAI: oai:DiVA.org:umu-22548DiVA: diva2:217071
ProjectsStress- och könshormoners verkningar på centrala nervsystemet