Developmental lead exposure impairs extinction of conditioned fear in young adult rats

摘要

Pavlovian fear conditioning is a model of emotional learning in which a neutral stimulus such as a tone is paired with an aversive stimulus such as a foot shock. Presentation of a tone with a foot shock in a context (test box) elicits a freezing response representative of stereotypic fear behavior. After conditioning has occurred, presentation of the context (test box) or tone in the absence of the unconditioned stimulus (shock) causes extinction of the fear response. Rats chronically exposed to environmentally relevant levels of lead (Pb²⁺) and controls were tested in a fear-conditioning (FC) paradigm at 50 days of age (PN50). Littermates to FC rats received an immediate shock (IS) when place in the test box with no tone. Blood Pb²⁺ levels in control and Pb²⁺-exposed animals were (mean ± sem): 0.76 ± 0.11 (n=15) and 25.8 ± 1.28 μg/dL (n=14). Freezing behavior was recorded during acquisition (day of training) or during 4 consecutive extinction days. Control and Pb²⁺-exposed FC rats exhibited the same level of freezing time on the acquisition day. No freezing behavior occurred in IS rats regardless of treatment. Presentation of context 24 hrs later produced a freezing response on both control and Pb²⁺-exposed FC rats but not in IS rats. When tested in the extinction phase, Pb²⁺-exposed FC rats exhibited deficits in extinction compared to control FC rats. That is, when presented with context on 4 consecutive days after acquisition of the fear response, Pb²⁺-exposed FC rats exhibited a greater freezing response than control FC rats. These findings indicate that chronic Pb²⁺ exposure produces a deficit in extinction learning and the animals remain more fearful than controls.