Lesions of the basolateral amygdala reverse the long-lasting interference with shuttle box escape produced by uncontrollable stress.
Exposure to an uncontrollable, but not a controllable, stressor produces a constellation of behaviors called learned helplessness. In rodents, uncontrollable stress interferes with the ability to learn to escape from escapable shocks delivered in a shuttle box. The stress-induced shuttle box escape deficit is a common screening tool for potential antidepressant strategies. Inconsistencies in the literature exist regarding the time-course of, and mechanisms underlying, stress-induced escape deficits. When no common cues are shared between the stressor and testing environment, the escape deficit is short lived and independent of conditioned freezing. In contrast, when stress and testing occur in the same or similar environments, the escape deficit is very long lasting. The current studies address the hypothesis that the long-lived escape deficit produced by uncontrollable stress is dependent upon conditioned fear and the basolateral amygdala (BLA). Rats received bilateral excitotoxic lesions of the BLA 2 weeks following uncontrollable foot shocks. One week after surgery, rats were tested for conditioned freezing and escape behavior in the same shuttle boxes in which prior foot shocks were delivered. Stressed rats with sham lesions displayed robust conditioned freezing and failed to escape during shuttle box testing. Lesions of the BLA eliminated conditioned freezing and completely restored stressed rats' ability to perform the escape contingency. These data indicate that the long-lived stress-induced escape deficit produced under conditions in which the stressor and testing environments share common cues is dependent upon conditioned freezing elicited by the BLA. Results have important implications for the mechanisms underlying learned helplessness phenomena.
Greenwood
Benjamin N
BN
Department of Integrative Physiology and The Center for Neuroscience, University of Colorado-Boulder, Campus Box 354, Boulder, CO 80309, United States. Ben.Greenwood@Colorado.edu
Strong
Paul V
PV
Fleshner
Monika
M
D000679:Amygdala / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003214:Conditioning, Classical; D004924:Escape Reaction / Q000502:physiology*; D005239:Fear / Q000502:physiology / Q000523:psychology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D006380:Helplessness, Learned; D007266:Inhibition, Psychological; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology; D013315:Stress, Psychological / Q000523:psychology*