Increased levels of conditioned fear and avoidance behavior coincide with 3 changes in phosphorylation of the protein kinase B (AKT) within the amygdala 4 in a mouse model of extremes in trait anxiety
| Authors | |
|---|---|
| Year of publication | 2012 |
| Type | Article in Periodical |
| Magazine / Source | Neurobiology of Learning and Memory |
| Citation | |
| Web | http://www.sciencedirect.com/science/article/pii/S1074742712000597 |
| Doi | http://dx.doi.org/10.1016/j.nlm.2012.04.009 |
| Field | Neurology, neurosurgery, neurosciences |
| Keywords | HAB; Selective breeding; Extinction; Spontaneous recovery; Startle; Hippocampus |
| Description | Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned 29 fear. To gain further insights into the mechanisms underlying these phenomenona, we studied condi- 30 tioned fear in mice originating form a bi-directional selective breeding approach, which is based on 31 elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxi- 32 ety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 33 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the baso- 34 lateral amygdala 45 min after conditioning. No similar changes were observed after non-associative 35 immediate shock presentations. Fear extinction of recent but not older fear memories was preserved. 36 However, HAB mice were more prone to relapse of conditioned fear with the passage of time. HAB mice 37 also displayed higher levels of contextual fear compared to NAB and LAB mice and exaggerated avoidance 38 following step-down avoidance training. Interestingly, HAB mice showed lower and LAB mice higher lev- 39 els of acoustic startle responses compared to NAB controls. The increase in arousal observed in LAB mice 40 coincided with the general absence of conditioned freezing. Taken together, our results suggest that the 41 genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic mem- 42 ories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards 43 passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking 44 behavior seems to be associated with an increase in active coping styles. Our data imply changes in 45 AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories. |