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Updated: May 6, 2026
The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
Modest elevation of corticosterone in preweanling rats impairs subsequent trace eyeblink conditioning during the
Dragana I Claflin1, Leslie R Greenfield, Michael B Hennessy
1Department of Psychology, Wright State University, 335 Fawcett Hall, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA.
Insights
Even modest elevations in corticosterone, a stress hormone, can impair hippocampus-dependent learning in young rats. This study shows physiological levels of corticosterone negatively affect associative learning.
Area of Science:
- Neuroscience
- Endocrinology
- Behavioral Science
Background:
- The hippocampus is vulnerable to glucocorticoid effects.
- Previous studies showed high corticosterone levels cause sex-specific learning deficits.
Purpose of the Study:
- To investigate the impact of physiologically relevant corticosterone levels on hippocampus-mediated learning.
- To use a more consistent drug delivery method (osmotic mini-pumps).
Main Methods:
- Young rats (15-day-old) received corticosterone or vehicle via osmotic mini-pumps for 3 days.
- Learning was assessed on Day 28 using trace eyeblink conditioning.
- Blood corticosterone levels were measured.
Main Results:
- A modest corticosterone elevation (11.77 μg/dl vs. 6.02 μg/dl) impaired learning.
- Significantly lower percentage and amplitude of conditioned responses (CRs) were observed.
- No significant differences in response timing, but a trend towards later CR onset and peak.
Conclusions:
- Physiologically relevant elevations in corticosterone can impair hippocampus-dependent learning.
- Even short-term exposure to elevated corticosterone has lasting effects.
- These findings highlight the sensitivity of the hippocampus to stress hormones during development.
Abstract:
The hippocampus is known to be especially sensitive to the deleterious effects of glucocorticoids. Previously, we administered exogenous corticosterone, the major stress-related glucocorticoid in rats, to young developing rats using subcutaneous pellets which produced high pharmacological levels of circulating corticosterone as well as a sex-specific learning deficit for males on a hippocampus-mediated associative learning task, trace eyeblink conditioning [1]. The present study evaluated the effects of corticosterone administered at a physiologically-relevant level by a more consistent release method, osmotic mini-pumps. Pumps were implanted subcutaneously in 15-day-old rats to deliver either corticosterone or the vehicle control (PEG) at a rate of 1 μl/h over 3 days. On Day 28, learning was assessed using trace eyeblink conditioning. The results of the present experiment revealed that a small elevation in corticosterone (11.77 μg/dl versus 6.02 μg/dl for controls) within the normal physiological range impaired learning as determined by a significantly lower percentage and amplitude of total conditioned responses (CRs) and lower amplitude of adaptive responses relative to the control group. There were no significant differences in response timing, although the corticosterone group tended to produce CRs which began and peaked a little later than controls. These findings indicate that even modest elevations of corticosterone for several days can produce later impairments on this hippocampally mediated learning task.
