title: The neurosteroid allopregnanolone impairs object memory and contextual fear memory in male C57BL/6J mice.
abstract: Allopregnanolone (ALLO, or 3α-hydroxy-5α-pregnan-20-one) is a steroid metabolite of progesterone and a potent endogenous positive allosteric modulator of GABA-A receptors. Systemic ALLO has been reported to impair spatial, but not nonspatial learning in the Morris water maze (MWM) and contextual memory in rodents. These cognitive effects suggest an influence of ALLO on hippocampal-dependent memory, although the specific nature of the neurosteroid's effects on learning, memory or performance is unclear. The present studies aimed to determine: (i) the memory process(es) affected by systemic ALLO using a nonspatial object memory task; and (ii) whether ALLO affects object memory via an influence within the dorsal hippocampus. Male C57BL/6J mice received systemic ALLO either before or immediately after the sample session of a novel object recognition (NOR) task. Results demonstrated that systemic ALLO impaired the encoding and consolidation of object memory. A subsequent study revealed that bilateral microinfusion of ALLO into the CA1 region of dorsal hippocampus immediately following the NOR sample session also impaired object memory consolidation. In light of debate over the hippocampal-dependence of object recognition memory, we also tested systemic ALLO-treated mice on a contextual and cued fear-conditioning task. Systemic ALLO impaired the encoding of contextual memory when administered prior to the context pre-exposure session. Together, these results indicate that ALLO exhibits primary effects on memory encoding and consolidation, and extend previous findings by demonstrating a sensitivity of nonspatial memory to ALLO, likely by disrupting dorsal hippocampal function.
authors.affiliation: Department of Psychology, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA.
authors.forename: Akiva
authors.initials: A
authors.lastname: Rabinowitz
authors.affiliation: Center for Complex Systems & Brain Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431-0991, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Veterans Affairs Medical Center, Portland Alcohol Research Center, 3710 SW U.S. Veterans Hospital Road, Portland, OR 97239, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Finn
authors.affiliation: Department of Psychology, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA; Center for Complex Systems & Brain Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431-0991, USA. Electronic address: rstackma@fau.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Stackman
mesh_terms: D000818:Animals; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D011280:Pregnanolone / Q000008:administration & dosage / Q000633:toxicity*; D011963:Receptors, GABA-A / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D018755:GABA Agonists; D012739:Gonadal Steroid Hormones; D011963:Receptors, GABA-A; D011280:Pregnanolone
keywords: Context; Fear conditioning; Hippocampus; Learning; Memory; Neurosteroid; Novelty; Object recognition