LeDoux Lab 2009 SfN Abstracts
 
Program#/Poster#: 479.22/FF123
Title: Terazosin, an alpha1-adrenergic receptor antagonist, enhances acquisition and impairs extinction of Pavlovian cue fear, but does not affect context fear
Location: South Hall A
Presentation Time: Monday, Oct 19, 2009, 2:00 PM - 3:00 PM
Authors: *S. C. LAZZARO, C. K. CAIN, J. E. LEDOUX;
Ctr. Neural Sci., New York Univ., New York, NY
Abstract: Norepinephrine (NE) is thought to play a key role in fear, but its role in Pavlovian fear conditioning, a major model for understanding the neural basis of fear, is poorly understood. In the present set of experiments, we examined the acquisition and extinction of Pavlovian cue fear, as well as context fear, after systemic injections of terazosin, a selective alpha-1 receptor antagonist (20mg/kg, i.p.), in rats. In our first experiment, rats were injected with terazosin prior to three tone-shock pairings. Terazosin-treated rats showed facilitated acquisition, with higher tone-elicited freezing during both the acquisition session and the 48-hr drug free test of long-term memory in a novel context. Terazosin-treated rats, however, showed no difference in context fear when returned to the fear conditioning chamber 3 hours later. In our second experiment, we examined the effect of terazosin on cue fear extinction by injecting terazosin before 20 non-reinforced tone presentations, 24 hours after acquisition. Terazosin-treated rats showed impaired extinction learning and no evidence of long-term extinction when tested drug-free 24 hours later. Previous experiments in our lab (Cain et al., SfN 2006) found similar findings with another alpha-1 receptor antagonist, prazosin. Terazosin may be more amenable to brain infusion studies, however, as it has a much higher water solubility and is a more selective alpha-1 receptor blocker.. Given that alpha-1 receptor activity in the amygdala is known to facilitate GABAergic transmission via a presynaptic mechanism (Braga et al, 2004), terazosin may be exerting its affects on extinction and acquisition by inhibiting GABA function, and thereby disinhibiting excitatory processing in amygdala fear circuits. We are currently investigating this possibility with microinfusions of terazosin directly into the amygdala prior to fear conditioning or extinction training.
Support: R37 MH038774
P50 MH058911
R01 MH046516
NRSA to C.K.C. (5F32MH077458-03)