Neurobiology of Learning and Memory 86 (2006) 123–132 www.elsevier.com/locate/ynlme 1074-7427/$ - see front matter  2005 Elsevier Inc. All rights reserved. doi:10.1016/j.nlm.2005.12.008 Enhancement of extinction memory consolidation: The role of the noradrenergic and GABAergic systems within the basolateral amygdala Daniel J. Berlau ¤ , James L. McGaugh Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA Received 6 December 2005; revised 19 December 2005; accepted 20 December 2005 Available online 3 February 2006 Abstract Evidence from previous studies indicates that the noradrenergic and GABAergic inXuences within the basolateral amygdala (BLA) modulate the consolidation of memory for fear conditioning. The present experiments investigated whether the same modulatory inXu- ences are involved in regulating the extinction of fear-based learning. To investigate this issue, male Sprague Dawley rats implanted with unilateral or bilateral cannula aimed at the BLA were trained on a contextual fear conditioning (CFC) task and 24 and 48 h later were given extinction training. Immediately following each extinction session they received intra-BLA infusions of the GABAergic antagonist bicuculline (50 ng), the -adrenocepter antagonist propranolol (500 ng), bicuculline with propranolol, norepinephrine (NE) (0.3, 1.0, and 3.0 g), the GABAergic agonist muscimol (125ng), NE with muscimol or a control solution. To investigate the involvement of the dorsal hippocampus (DH) as a possible target of BLA activation during extinction, other animals were given infusions of muscimol (500 ng) via an ipsilateral cannula implanted in the DH. Bilateral BLA infusions of bicuculline signiWcantly enhanced extinction, as did infusions into the right, but not left BLA. Propranolol infused into the right BLA together with bicuculline blocked the bicuculline-induced memory enhancement. Norepinephrine infused into the right BLA also enhanced extinction, and this eVect was not blocked by co-infusions of muscimol. Additionally, muscimol infused into the DH did not attenuate the memory enhancing eVects of norepinephrine infused into the BLA. These Wndings provide evidence that, as with original CFC learning, noradrenergic activation within the BLA modulates the con- solidation of CFC extinction. The Wndings also suggest that the BLA inXuence on extinction is not mediated by an interaction with the dorsal hippocampus.  2005 Elsevier Inc. All rights reserved. Keywords: Bicuculline; Norepinephrine; Propranolol; Muscimol; Hippocampus; Contextual fear conditioning 1. Introduction Contextual fear conditioning (CFC) is induced by pairing a context (conditioned stimulus; CS) with a fear-inducing stimulus (unconditioned stimulus; US), usually footshock. Subsequent elicitation of autonomic and behavioral fear responses, such as freezing, by the CS is typically used as an index of the CS–US association (Blanchard & Blanchard, 1972). CFC responses, like other forms of learned responses, can be extinguished by presenting the CS alone. The new information that the context no longer predicts a footshock results in a decrease in the expression of the conditioned response (CR) (Pavlov, 1927). Extinction shares many com- mon properties with original learning. Both require the for- mation of CS–US predictions and both require consolidation to achieve stability (McGaugh, 2000). Considerable evidence indicates that the basolateral nucleus of the amygdala (BLA) plays an important role in modulating the consolidation of fear-based memories, including CFC (Berlau & McGaugh, 2003; HuV, Wright-Hardesty, Higgins, Matus-Amat, & Rudy, 2005; Kim & Jung, 2005; LaLumiere, Buen, & McGaugh, 2003; McGaugh, 2002; Vazdarjanova & McGaugh, 1999; Wilensky, Schafe, & LeDoux, 2000). There is extensive evi- dence that post-training noradrenergic agonists and antag- onists enhance and impair, respectively, the consolidation * Corresponding author. Fax: +1 949 824 2952. E-mail address: danb@uci.edu (D.J. Berlau).