[Abstract Title]. - Society for Neuroscience

Center for Behavioral Neuroscience NSF agreement #IBN-9876754
FACES NSF Award #0450303 Subaward # I-66-606-63
Title: Systemic rapamycin disrupts the consolidation of context but not cued fear memory
Authors: *E. M. GLOVER 1 , M. DAVIS 2 ;
1 Dept Psychol, Ctr. Behav Neurosci, Emory Univ., Atlanta, GA; 2 Dept Psychiat & Behavioral
Sci., Emory Univ. Sch. Med., Atlanta, GA
Abstract: The mammalian target of rapamycin (mTOR) kinase regulates protein synthesis.
Rapamycin, an mTOR kinase inhibitor, was recently shown to disrupt the consolidation of toneshock
and context-shock fear memories (assessed with freezing) when infused into the amygdala
(Parsons et al., 2006) immediately after training, and also context-shock memories (also assessed
with freezing) when injected systemically either before or after training (Blundell et al., 2008).
Because rapamycin is centrally active following systemic administration and is FDA-approved
for use in humans, it has recently attracted interest as a possible prophylactic treatment for
PTSD-associated fear memories. To evaluate the generality of rapamycin effects on fear memory
consolidation, we assess here the effects of systemic rapamycin injections on the consolidation of
odor-shock and context-shock fear memories using fear-potentiated startle (FPS) as an
alternative fear measure. On each of 2 consecutive days, rats received a pre-conditioning test
during which their startle response to 30 95-dB noise bursts (noise alone test trial) was measured.
Twenty-four hours later, they were returned to the chamber where they received a single 4-sec
odor stimulus (5% amyl acetate) and co-terminating footshock (0.4 mA, 0.5-sec) and,
immediately afterwards, an i.p. injection of either rapamycin (40 mg/kg) or vehicle. 7 days later,
they were returned to test cage where they received 70 startle-eliciting noise bursts, of which 10
of the final 40 were preceded by the odor conditioned stimulus. For some rats, the training and
test contexts were identical. For others, the test context was altered (i.e., sandpaper inserts over
the shock bars, Velcro on the sides, and 2 chains suspended from the top). Rapamycin
significantly reduced FPS to the context CS (calculated as the percent change in startle from the
pre-training test to the initial 30 noise alone trials of the post-conditioning test) but, in contrast to
Parsons et al. (2006), did not reduce FPS to the discrete cue CS (calculated as the percent change
in startle amplitude from noise alone to odor-noise test trials). This may reflect the different
modalities used in these two studies (i.e., tone vs. odor) or, alternatively, a greater sensitivity of
discrete cue fear conditioning to intra-amygdala vs. systemic rapamycin administration - a result
similar to that seen with many other systemically administered compounds which selectively
disrupt hippocampal-dependent (i.e., context fear or inhibitory avoidance) but not hippocampalindependent
fear memories. If the latter, then this selectivity may limit the effectiveness of
mTOR inhibitors as a PTSD treatment.
Disclosures: E.M. Glover, None; M. Davis, None.
Poster