Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala
Open Access
- 24 October 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (10), e26582
- https://doi.org/10.1371/journal.pone.0026582
Abstract
Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.Keywords
This publication has 70 references indexed in Scilit:
- Thyroid hormone regulation by stress and behavioral differences in adult male ratsHormones and Behavior, 2011
- Stress, memory and the amygdalaNature Reviews Neuroscience, 2009
- Levothyroxin restores hypothyroidism‐induced impairment of hippocampus‐dependent learning and memory: Behavioral, electrophysiological, and molecular studiesHippocampus, 2008
- Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin studyJournal of Psychiatric Research, 2008
- Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studiesMolecular Psychiatry, 2008
- Posttraining Glucocorticoid Receptor Agonist Enhances Memory in Appetitive and Aversive Pavlovian Discrete-Cue Conditioning ParadigmsNeurobiology of Learning and Memory, 2002
- De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder.Journal of Abnormal Psychology, 2000
- Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.Behavioral Neuroscience, 1992
- Naloxone and shock-elicited freezing in the rat.Journal of Comparative and Physiological Psychology, 1979
- The conditioned emotional response as a function of intensity of the US.Journal of Comparative and Physiological Psychology, 1961