Both α₁‐ and β₁‐adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

Abstract

BACKGROUND AND PURPOSE The bed nucleus of the stria terminalis (BNST) is a limbic structure that is involved in the expression of conditioned contextual fear. Among the numerous neural inputs to the BNST, noradrenergic synaptic terminals are prominent and some evidence suggests an activation of this noradrenergic neurotransmission in the BNST during aversive situations. Here, we have investigated the involvement of the BNST noradrenergic system in the modulation of behavioural and autonomic responses induced by conditioned contextual fear in rats. EXPERIMENTAL APPROACH Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (6 footshocks, 1.5 ma/ 3 s). Twenty‐four hours later freezing and autonomic responses (mean arterial pressure, heart rate and cutaneous temperature) to the conditioning box were measured for 10 min. The adrenoceptor antagonists were administered 10 min before the re‐exposure to the aversive context. KEY RESULTS L‐propranolol, a non‐selective β‐adrenoceptor antagonist, and phentolamine, a non‐selective α‐adrenoceptor antagonist, reduced both freezing and autonomic responses induced by aversive context. Similar results were observed with CGP20712, a selective β1‐adrenoceptor antagonist, and WB4101, a selective α1‐antagonist, but not with ICI118,551, a selective β2‐adrenoceptor antagonist or RX821002, a selective α2‐antagonist. CONCLUSIONS AND IMPLICATIONS These findings support the idea that noradrenergic neurotransmission in the BNST via α1‐ and β1‐adrenoceptors is involved in the expression of conditioned contextual fear.

Role of bed nucleus of the stria terminalis and amygdala AMPA receptors in the development and expression of context conditioning and sensitization of startle by prior shock

“…Indeed, results from several studies (Hott et al 2012; Luyten et al 2011; Resstel et al 2008; Sullivan et al 2004) that have used lesion or other inactivation procedures to disrupt BNST function, and a variety of behavioral and autonomic measures to assess fear, indicate that it is involved. Even NBQX was found to disrupt freezing to a shock-associated context in Zimmerman and Maren (2011).…”

“…CRF (Lee and Davis 1997), calcitonin gene-related peptide (CGRP) (Sink et al 2011, 2013), and pituitary adenylate cyclase-activating peptide (PACAP) (Hammack et al 2009) each increase startle when infused into the BNST and produce other hyper-arousal/anxiety-like effects as well (e.g., Lee et al 2008; Ciccocioppo et al 2003; Sahuque et al 2006; Hammack et al 2010; Sink et al 2013). Research by Morilak and colleagues (c.f., Morilak et al 2003) has pointed to a possible role for galanin, and still others have identified a role for norepinephrine (Deyama et al 2008, 2009; Fendt et al 2005; Hott et al 2012; Schweimer et al 2005), which is found in the BNST at concentrations higher than almost any other brain area (Brownstein et al 1974; Kilts and Anderson 1986). These particular systems are likely to be only the tip of a very large iceberg, with the unique neurochemical makeup of the BNST and its afferents providing as-of-yet unmined opportunities to target with greater precision the most devastating symptoms of acute- and post-traumatic stress disorder, and possibly other anxiety conditions.…”

CGRP antagonist infused into the bed nucleus of the stria terminalis impairs the acquisition and expression of context but not discretely cued fear

“…Indeed, the majority of studies that have implicated the BNST in conditioned fear have done so using long-duration fear stimuli such as shock-or withdrawalassociated contexts (Aston-Jones et al 1999;Resstel et al 2008;Luyten et al 2011Luyten et al , 2012Ali et al 2012;Hott et al 2012). Several such studies have directly compared the effects of BNST manipulations on fear evoked by short-duration cues to fear evoked by longer-duration contextual (Sullivan et al 2004;Zimmerman and Maren 2011) .…”

Dorsolateral periaqueductal gray matter CB1 and TRPV1 receptors exert opposite modulation on expression of contextual fear conditioning

“…When rats are later re-exposed to the context, now referred to as the conditioned stimulus, they exhibit freezing behavior and increased autonomic activity, represented by increased mean arterial pressure (MAP) and heart rate (HR) and decreased cutaneous temperature (CT) (Fabri et al, 2014;Hott et al, 2012). The behavioral and autonomic changes are collectively called conditioned emotional response (Resstel et al, 2006).…”