Dorsal hippocampal progesterone infusions enhance object recognition in young female mice

Abstract

The effects of progesterone on memory are not nearly as well studied as the effects of estrogens. Although progesterone can reportedly enhance spatial and/or object recognition in female rodents when given immediately after training, previous studies have injected progesterone systemically, and therefore, the brain regions mediating this enhancement are not clear. As such, this study was designed to determine the role of the dorsal hippocampus in mediating the beneficial effect of progesterone on object recognition. Young ovariectomized C57BL/6 mice were trained in a hippocampal-dependent object recognition task utilizing two identical objects, and then immediately or 2 hrs afterwards, received bilateral dorsal hippocampal infusions of vehicle or 0.01, 0.1, or 1.0 μg/μl water-soluble progesterone. Forty-eight hours later, object recognition memory was tested using a previously explored object and a novel object. Relative to the vehicle group, memory for the familiar object was enhanced in all groups receiving immediate infusions of progesterone. Progesterone infusion delayed 2 hrs after training did not affect object recognition. These data suggest that the dorsal hippocampus may play a critical role in progesterone-induced enhancement of object recognition.

Regulation of object recognition and object placement by ovarian sex steroid hormones

“…However, P 4 administered systemically (4–20 mg/kg) immediately after training dose-dependently enhances OR in young ovariectomized female rodents [127; 129; 144; 165–167]. These effects are supported by other work from our laboratory in which 0.01, 0.1, or 1 μg P 4 infused directly into the dorsal hippocampus enhanced OR in a manner dependent on rapid hippocampal cell signaling [87; 168]. …”

“…Clearly, more research is needed on this subject. Finally, P 4 must be within two hours after object training in order to facilitate object memory consolidation [129; 144; 168], supporting the role of P 4 in mediating memory formation during the memory consolidation window.…”

Modeling menopause: The utility of rodents in translational behavioral endocrinology research

“…We and many others have investigated the effects of dose, task-specific effects, type of hormone, menopause type, as well as route, timing, and duration of treatment administration on both brain and behavior in female rodents [43–45, 113–121]. …”

Trajectories and phenotypes with estrogen exposures across the lifespan: What does Goldilocks have to do with it?

“…The Morris water maze is traditionally a measure of spatial reference memory, but many laboratories have altered the paradigm to evaluate working memory, the use of distal and proximal cues, and room geometry and cue learning (Pearce et al, 1998; Clark et al, 2007). Other tasks including, but not limited to, the T maze, Y maze, delayed-match-to-sample, novel object recognition, and place recognition have also been used to quantify hormone effects on learning and memory performance in rodents (Bimonte-Nelson et al, 2015; Chisholm and Juraska, 2012; Daniel et al, 2005; Foster et al, 2003; Frick and Gresack, 2003; Gibbs, 2002; Gibbs et al, 2009; Johnson et al, 2002; Nelson et al, 2012; Orr et al, 2009). Many of the experiments discussed in this review utilize a battery of these tasks to evaluate the effects of gonadal hormones on rodent cognition.…”

“…It is also noteworthy that administration of allopregnanolone, a progesterone metabolite, was detrimental to episodic memory, but not semantic or working memory, in healthy women (Kask et al, 2008), and it impaired spatial reference memory in young rats (Frye and Sturgis, 1995; Johansson et al, 2002). However, there are many studies showing that progesterone can enhance some cognitive measures in rodents, mostly in the realm of non-spatial memory (Frye et al, 2007; Frye and Walf, 2008; Harburger et al, 2008; Lewis et al, 2008; Orr et al, 2009). The mechanisms of both the detrimental and enhancing effects of progestogens are currently being deciphered in the field, and the work in this area is noteworthy and convincing (Braden et al, 2011, 2010; Fortress et al, 2014; Harburger et al, 2009; Orr et al, 2012; for review see: Singh and Su, 2013a, 2013b).…”