Nicotine enhances trace cued fear conditioning but not delay cued fear conditioning in C57BL/6 mice

Nicotine facilitates hippocampus-dependent contextual but not hippocampus-independent cued delay fear conditioning. To test if the effects of nicotine are specific to contextual fear conditioning or would extend to another hippocampus-dependent version of fear conditioning, we compared the effects of nicotine on cued delay and cued trace fear conditioning in male and female C57BL/6 mice. Unlike cued delay fear conditioning, cued trace fear conditioning is hippocampus dependent. Thus, if nicotine enhances hippocampus-dependent fear conditioning, nicotine should enhance trace fear conditioning. For both trace and delay conditioning, five 30s, 85 dB white noise conditioned stimuli (CS) were paired with five 2s, 0.5 mA footshock unconditioned stimuli (US). In the trace paradigm, a 30-s period was inserted between CS offset and US onset. The CS and US co-terminated in the delay paradigm. Testing occurred 24 It later. The data indicate that nicotine (given on training and testing day) enhances trace but not delay cued fear conditioning. No sex differences were found. For delay cued fear conditioning a high level of freezing to the CS was found. Thus, a second experiment examined if the lack of enhancement of delay cued fear conditioning by nicotine was due to a ceiling effect. The CS duration was decreased to 15s and only one CS-US pairing was used for delay and trace cued fear conditioning. Although overall levels of freezing to the cue were lower in the second experiment, nicotine still enhanced trace fear conditioning but did not enhance delay fear conditioning. Taken together, the results of the present experiments suggest that nicotine enhances hippocampus-dependent versions of fear conditioning. (C) 2004 Elsevier B.V. All rights reserved.