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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. [ABSTRACT FROM AUTHOR]

Background and purpose:Pregabalin, which binds to the α2-δ subunit of voltage-gated calcium channels, increased the threshold for pain during colorectal distension (CRD) in irritable bowel syndrome (IBS) patients. We tested the effects of oral pregabalin on the visceral pain-related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats.Experimental approach:The activity of the abdominal musculature (viscerosomatic response), monitored by electromyography and intracolonic manometry, and changes in blood pressure and heart rate, monitored by telemetry, were assessed simultaneously in conscious rats during CRD.Key results:Pregabalin (10–200 μmol kg−1, p.o.) inhibited dose dependently the viscerosomatic response to phasic, noxious CRD (12 distensions at 80 mm Hg). At 200 μmol kg−1, pregabalin also reduced the increase in blood pressure and heart rate associated with noxious CRD. Moreover, pregabalin (200 μmol kg−1, p.o.) reduced the visceromotor response to ascending phasic CRD (10–80 mm Hg) and significantly increased the threshold pressure for response. During phasic CRD (2–20 mm Hg), pregabalin (200 μmol kg−1, p.o.) increased intracolonic volume, resulting in a shift to the left of the pressure–volume relationship curve, indicative of an increase of compliance.Conclusions and implications:Pregabalin reduced the viscerosomatic and autonomic responses associated with CRD-induced visceral pain and increased colonic compliance in rats. These observations confirm the analgesic activity of pregabalin on visceral pain and support the translational value of the CRD model to humans. Ligands for the α2-δ subunit might represent interesting compounds for the treatment of visceral pain disorders, such as IBS.British Journal of Pharmacology (2008) 155, 407–416; doi:10.1038/bjp.2008.259; published online 23 June 2008 [ABSTRACT FROM AUTHOR]