[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 283.22/PP18
Topic: E.06.f. Stress modulated pathways
Support: MH60706
5T32 E507148
NIEHS P30 ES05022
Title: Effects of intermittent pairing of chronic restraint stress with footshock on habituation of
the c-fos response in the mouse brain
Authors: *A. W. KUSNECOV 1 , D. URBACH-ROSS 2 ;
1 Dept Psychol, 2 Toxicology, Rutgers Univ., Piscataway, NJ
Abstract: It has been shown in rats that the c-Fos response habituates during chronic restraint
stress. Habituation is considered a learning process, and in the case of restraint, predictable
“safe” outcomes (eg., returning to home cage) following restraint may contribute to diminished
c-Fos responses. The current study tested this question using male C57BL/6 mice about which
little is known concerning habituation of c-Fos expression to chronic stress. Specifically, we
asked if the c-fos response to repeated restraint would be attenuated if restraint sessions were
intermittently followed by a session of unpredictable footshock. As a result, it was expected that
restraint sessions would not always predict return to a safe, home cage environment, but rather
may be followed by relocation of the mouse to the shock chamber. Mice were placed for 90 mins
daily into aerated 50 ml conical tubes for one (acute restraint) or ten days (chronic restraint),
while controls remained in the home cage. Of the chronically restrained mice, on Days 1, 4, 6, 7
and 9 of restraint, one group was returned to the home cage, while another was transferred to
separate chambers and received five 0.2 mA footshocks over a 15 min period before going to the
home cage. On the assessment day (D11), mice were perfused for brain c-Fos
immunohistochemistry after receiving restraint (Rst + Sh - test Rst; Rst+HC - test Rst) or home
cage (Rst + Sh - test HC). In addition to separate HC groups that were tested for acute restraint
effects, a group that received shock immediately before sacrifice after chronic restraint stress was
included (Rst+HC - test Sh). The results showed that chronic restraint produced a habituated, but
increased c-Fos response in the paraventricular nucleus, lateral septum, bed nucleus of the stria
terminalis, and the central nucleus of the amygdala. Surprisingly, pairing restraint with shock did
not block the attenuation in these areas. Interestingly, a heterotypic stressor (viz., shock) given
after chronic restraint (Rst + HC) dramatically elevated c-Fos in hippocampal CA1 and CA3,
whereas this was not evident after acute or chronic restraint. This suggests that these particular
areas may be less susceptible to activation under mild stress conditions but become activated
after a severe stressor such as shock. In conclusion, mice showed an elevated, but attenuated c-
Fos response in stress-related circuitry in response to repeated restraint. This attenuation was not
changed when the restraint was paired with shock. Therefore, the restraint itself did not appear to
serve as a conditioned stimulus to anticipate shock.
Disclosures: A.W. Kusnecov, None; D. Urbach-Ross, None.