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. Author manuscript; available in PMC: 2015 May 1.
Published in final edited form as: Pharmacol Ther. 2014 Dec 27;149:150–190. doi: 10.1016/j.pharmthera.2014.12.004

Table 3.

Noradrenergic (NE) signaling in fear extinction (preclinical studies).

Drug/manipulation Extinction learning Extinction retrieval Longterm extinction Route Reference
Enhancing noradrenergic signaling
Noradrenaline ns + ns icv (Merlo and Izquierdo, 1967)
Methylphenidate + + ns ip (Abraham et al., 2012)
Noradrenaline ns +1 ns BLA (Berlau and McGaugh, 2006)
ns No effect1 ns BLA (Fiorenza et al., 2012)
ns No effect1 ns CA1 (Fiorenza et al., 2012)
ns −1 ns IL (Fiorenza et al., 2012)
Atomoxetine (NE reuptake inhibitor) ns No effect6 + (SR)5 systemic (Janak and Corbit, 2011)
Isoproterenol (β ag) No effect ns ns ip (subchronic) (Do-Monte et al., 2010b)
ns (+)1 ns ip (subchronic) (Do-Monte et al., 2010b)
ns (+)1 ns mPFC (Do-Monte et al., 2010b)
Yohimbine (α2 ant)8 + ns ns sc (Cain et al., 2004)
ns No effect1 ns sc (Cain et al., 2004)
+#2 +2 ns sc (Cain et al., 2004)
+ + − ip (Morris and Bouton, 2007)
No effect7 No effect ns ip (Mueller et al., 2009)
ns +* ns ip (Hefner et al., 2008)
ns No effect6 + (SR)5 systemic (Janak and Corbit, 2011)
Atipamezole (α2 ant)8 ns No effect4 ns sc (Davis et al., 2008)
Inhibiting noradrenergic signaling
Prazosine (α1 ant) ns No effect1 ns ip (subchronic) (Do-Monte et al., 2010a)
− ns ns ip (subchronic) (Do-Monte et al., 2010a)
− ns ns intra-mPFC (Do-Monte et al., 2010a)
Propanolol (β ant) No effect ns ns sc (Cain et al., 2004)
ns No effect1 ns sc (Cain et al., 2004)
No effect2 (−)3 ns sc (Cain et al., 2004)
(+)# No effect ns ip (Rodriguez-Romaguera et al., 2009)
− − ns ip (subchronic) (Do-Monte et al., 2010b)
ns No effect1 ns ip (subchronic) (Do-Monte et al., 2010b)
Atenolol (β ant) − ns ns mPFC (Do-Monte et al., 2010b)
ns No effect1 ns mPFC (Do-Monte et al., 2010b)
Sotalol (β ant) No effect No effect ns ip (Rodriguez-Romaguera et al., 2009)
Timolol (β ant) ns +1 ns BLA (Fiorenza et al., 2012)
Propanolol (β ant) No effect − ns IL (Mueller et al., 2008)
ns No effect1 ns IL (Mueller et al., 2008)
Timolol (β ant) ns +1 ns IL (Fiorenza et al., 2012)
ns No effect1 ns CA1 (Fiorenza et al., 2012)
1

Drug administration following extinction training;

2

spaced CS extinction, US = 0.7mA;

3

spaced CS extinction when US = 0.4mA; no effect when US = 0.7mA,

4

cocaine-conditioned place preference,

5

4 weeks,

6

instrumental lever press response,

7

reduced fear expression at start of extinction training, if extinction is performed in the same context as conditioning,

8

note that the net effect of α2 blockade is enhancement of noradrenergic signaling (see text).

*

Facilitates rescue of impaired fear extinction;

**

facilitates extinction of remote memories,

***

only in older animals (7 months), younger ones (2 months) are not affected

#

reduced fear expression at the beginning of extinction training.

+, Improved; -, impaired; (+) or (−), only minor effects; ip, intraperitoneal injection; injection; sc, subcutanous injection; icv, intracerebroventricular injection; ns, not studied; HPC, intra-hippocampal administration; BLA, intra-basolateral amygdala administration; IL, infralimbic cortex; PL, prelimbic cortex; CA1, cornu ammonis 1; Ren, Fear renewal; SR, spontaneous recovery; Re-in, reinstatement; ag, agonist; ant, antagonist, KO, knock-out; # reduced fear expression at start of extinction training.