| LeDoux Lab 2010 SfN Abstracts |
|---|
| Program#/Poster#: | 914.26/MMM42 |
| Title: | Propranolol rescues active avoidance behavior in rats exhibiting high freezing and poor avoidance |
| Location: | Halls B-H |
| Presentation Time: | Wednesday, Nov 17, 2010, 2:00 PM - 3:00 PM |
| Authors: | *C. K. CAIN1,2,
G. LAZARO-MUNOZ1, J. E. LEDOUX1,2; 1Ctr. for Neural Sci., New York Univ., NEW YORK, NY; 2Emotional Brain Inst., Nathan Kline Inst. for Psychiatric Res., Orangeburg, NY |
| Abstract: | In active avoidance (AA), rats learn
to emit an instrumental response in the presence of threatening conditional
stimuli (CSs) in order to prevent delivery of painful unconditional stimuli
(USs). Early in AA training, rats have no knowledge of the instrumental
contingency and fail to respond. This results in a conditioning trial where
CSs are paired with the US and subsequently trigger Pavlovian reactions
such as freezing. In order to acquire the active instrumental AA response,
rats must suppress this freezing response. Although it is currently unknown
how this freezing suppression occurs during AA training, recent findings
from our laboratory indicate that abolishing freezing can rescue AA in rats
that show poor AA performance. Specifically, rats showing high levels of
freezing and low levels of AA after 10 Sidman AA training sessions were
given electrolytic lesions of the central amygdala, a region known to mediate
Pavlovian freezing. After the lesions, freezing in the AA context was abolished
and AA performance was rescued (Lazaro-Munoz et al, 2010). Avoidance is a hallmark of anxiety disorders mainly because victims of trauma often adopt avoidance responses that interfere with daily living. However, therapists often attempt to instill active coping responses in traumatized patients that do not interfere with daily living. This sort of learning may be ideally modeled by AA training where subjects must learn to suppress maladaptive Pavlovian reactions and acquire adaptive instrumental actions in the face of fear. We sought to evaluate a human treatment option in our rat AA model that did not involve brain lesions. Beta adrenergic receptor blockers have been safely used for decades in humans for a variety of conditions. In particular, beta blockers are very effective for the treatment of stage-fright, where subjects have trouble performing because of Pavlovian fear reactions like freezing. Beta blockers have also been reported to impair freezing expression in rats when there is a competing motivation to act (Rodriguez-Romaguera et al, 2009). We trained rats using a Sidman AA procedure for 10 sessions and identified poor performers as previously described (Lazaro-Munoz et al, 2010). Prior to session 11, half of the poor performing rats were injected with propranolol (10 mg/kg) and half with saline. AA and freezing were assessed. Propranolol treatment produced a 50% reduction in freezing and led to a 5-fold increase in AA responding, effectively rescuing AA in the first post-injection session. These results suggest that beta blockers may facilitate AA and the acquisition of active coping strategies in humans. |
| Support: | NIH Grant MH077458 NIH Grant MH046516 NIH Grant MH086294 |