Fear Conditioning Effects on Sensitivity to Drug Reward

Abstract : The overall hypothesis is that mice undergoing repeated exposure to an aversive stimulus that is paired with neutral cues would develop ongoing fear responses (freezing behavior) to these cues, enhanced approach responses to drug associated contexts, and neural plasticity in relevant brain regions. Mice demonstrated freezing behaviors over 80% of the time when exposed to the context and tone cues (vs. 10% freezing behavior in the control group). In addition, fear extinction trials (20/day) employing repeated exposure to the context and tone cues without footshock administration abolished freezing behavior in previously fear-conditioned mice. Moreover, fosB levels were elevated by more than a third in the prelimbic and infralimbic cortices of fear extinguished mice. After place conditioning, both sham and fear conditioned mice exhibited a robust preference for the morphine associated side. Thus, fear extinction produces activation of neural plasticity factors in pre- and infralimbic cortices but acquisition of conditioned fear did not alter subsequent acquisition of conditioned opiate reward. This innovative approach will identify neural mechanisms and treatment approaches for post-traumatic stress disorder and addiction.