Delayed effects of cortisol enhance fear memory of trace conditioning.
Corticosteroids induce rapid non-genomic effects followed by slower genomic effects that are thought to modulate cognitive function in opposite and complementary ways. It is presently unknown how these time-dependent effects of cortisol affect fear memory of delay and trace conditioning. This distinction is of special interest because the neural substrates underlying these types of conditioning may be differently affected by time-dependent cortisol effects. Delay conditioning is predominantly amygdala-dependent, while trace conditioning additionally requires the hippocampus. Here, we manipulated the timing of cortisol action during acquisition of delay and trace fear conditioning, by randomly assigning 63 men to one of three possible groups: (1) receiving 10mg hydrocortisone 240 min (slow cort) or (2) 60 min (rapid cort) before delay and trace acquisition, or (3) placebo at both times, in a double-blind design. The next day, we tested memory for trace and delay conditioning. Fear potentiated startle responses, skin conductance responses and unconditioned stimulus expectancy scores were measured throughout the experiment. The fear potentiated startle data show that cortisol intake 240 min before actual fear acquisition (slow cort) uniquely strengthened subsequent trace conditioned memory. No effects of cortisol delivery 60 min prior to fear acquisition were found on any measure of fear memory. Our findings emphasize that slow, presumably genomic, but not more rapid effects of corticosteroids enhance hippocampal-dependent fear memories. On a broader level, our findings underline that basic experimental research and clinically relevant pharmacological treatments employing corticosteroids should acknowledge the timing of corticosteroid administration relative to the learning phase, or therapeutic intervention.
Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands; Priority Program Brain and Cognition, University of Amsterdam, The Netherlands. Electronic address: sandra.cornelisse@gmail.com.
Sandra
S
Cornelisse
Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Kapittelweg 29, 6525, EN The Netherlands. Electronic address: v.vanast@donders.ru.nl.
Vanessa A
VA
van Ast
Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands; Priority Program Brain and Cognition, University of Amsterdam, The Netherlands.
Marian
M
Joëls
Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands; Priority Program Brain and Cognition, University of Amsterdam, The Netherlands.
Merel
M
Kindt
D000328:Adult; D003213:Conditioning, Psychological / Q000187:drug effects*; D003463:Cues; D004311:Double-Blind Method; D005239:Fear / Q000187:drug effects*; D006185:Habituation, Psychophysiologic; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
D006854:Hydrocortisone
Cortisol; Fear conditioning; Fear potentiated startle; Memory; PTSD; Trace and delay