This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this study is to develop a way to measure inhibition of fear in rhesus monkeys and humans. In rats we have developed such a procedure in which one pair of cues (AX+) is paired with an aversive airblast and another pair of cues (BX-) is not paired with an aversive airblast. Under these conditions, rats learn to be afraid of A, not to be afraid of B and fear of X is some where in the middle. Importantly, when we test fear to A in the presence of B we see that B inhibits fear to A. We have set up the AX+, BX- discrimination in humans and are testing it in patients with post-traumatic stress disorder. We found that patients with PTSD do not show normal conditioned inhibition which means we have an objective measure of one of the core symptoms of PTSD, namely the inability to feel safe. In addition, we set up the AX+, BX- in rhesus monkeys at Yerkes and are now testing it in monkeys who have had separation from their mothers for brief periods of time during development as well as in monkeys that have had lesions of various brain areas. We found that lesions of the amygdala in rhesus monkeys block acquisition but expression of fear-potentiated startle, in contrast to rats, that should a blockade of both.
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