The Effect of Glucose on Hippocampal-Dependent Contextual Fear Conditioning

Abstract

The metabolic challenge of trauma disrupts hippocampal functioning, which is necessary for processing the complex co-occurring elements comprising the traumatic context. Poor contextual memory of trauma may subsequently contribute to intrusive memories and overgeneralization of fear. Glucose consumption following trauma may be a means to protect hippocampal functioning and contextual fear learning. This study experimentally examined the effect of glucose on hippocampal-dependent contextual learning versus cued fear learning in humans. Forty-two male participants underwent cued conditioning with an unconditional stimulus (US) (shock) paired with a discrete conditional stimulus (geometric shape) and context conditioning (requiring hippocampal processing) with a US unpredictably paired with a background context (picture of room). Participants were then blindly randomized to consume either a 25 g glucose or sweet-tasting placebo drink and returned for a test phase 24 hours later. Measures included acoustic startle response, US expectancy, blood glucose levels, and arousal ratings. The glucose group showed superior retention of hippocampal-dependent contextual learning at test relative to the placebo group, as demonstrated by acoustic startle response and US expectancy ratings. Glucose and placebo groups did not differ on any measure of cued fear learning at test. This study provides experimental evidence that in mildly stressed humans postconditioning glucose consumption improves retention of hippocampal-dependent contextual learning but not cued learning. Ultimately, glucose consumption following trauma may be a means of improving learning about the traumatic context, thereby preventing subsequent development of symptoms of posttraumatic stress.