Neurosteroids affect spatial/reference, working, and long-term memory of female rats

Area of Science:

• Neuroscience
• Endocrinology
• Behavioral Pharmacology

Background:

• Female rats exhibit slower spatial task acquisition during estrus when GABA-active progesterone is elevated.
• Neurosteroids and neuroactive steroids (neuro(active) steroids) interact with GABA receptor complexes (GBRs).

Purpose of the Study:

• To investigate the activational effects of various neuro(active) steroids on spatial/reference, working, and long-term memory in female rats.
• To determine if these effects are mediated through GABA receptor complexes (GBRs).

Main Methods:

• Ovariectomized Long-Evans rats (N=107) received subcutaneous injections of six neuro(active) steroids or vehicle.
• Rats were subsequently tested in the Morris water maze, Y maze, and open field test.
• A subset of rats (N=75) received intracerebroventricular (ICV) implants of neuro(active) steroids or cholesterol vehicle and underwent similar behavioral testing.

Main Results:

• Neuro(active) steroid administration, particularly THP and DHEAS, decreased distances to the hidden platform in the Morris water maze.
• THP and DHEAS demonstrated differential effects on spatial and working memory tasks, with dose-dependent impacts on accuracy and latency.
• No significant changes in open field behavior (motoricity/anxiolysis) were observed across neuro(active) steroid treatments.

Conclusions:

• The neurosteroids THP and DHEAS significantly influenced spatial/reference, working, and long-term memory in ovariectomized rats.
• These memory effects were independent of alterations in motor activity or anxiety levels.
• Neuro(active) steroids acting at GBRs play a crucial role in modulating cognitive functions in female rodents.