Corticotropin-Releasing Factor Receptor 1 and Central Heart Rate Regulation in Mice during Expression of Conditioned Fear

Abstract

The present study was performed to 1) determine heart rate (HR) effects mediated through central corticotropin-releasing factor receptor subtypes 1 (CRF 1 ) and 2 (CRF 2 ) and 2) to investigate the contribution of endogenous CRF to baseline HR and its fear-induced adjustment in freely moving mice. CRF ligands were injected into both lateral ventricles (i.c.v.) 15 min before the presentation of a conditioned auditory fear stimulus (CS). Initial behavioral results suggest an ovine CRF (oCRF)-mediated enhanced baseline fear and mildly enhanced conditioned auditory fear. In contrast, i.c.v. injection of oCRF (35-210 ng/mouse) dose-dependently decreased baseline HR, increased HR variability, and attenuated the CS-induced tachycardia. This effect is suggested to depend on a combined activation of sympathetic and parasympathetic activity referred to as enhanced sympathovagal antagonism. An extreme bradycardia was elicited by oCRF injection into the lower brainstem. All HR effects were probably mediated by CRF 1 because injection of the CRF 2 -selective agonist mouse urocortin II was ineffective, and the baseline bradycardia by i.c.v. CRF was preserved in CRF 2 -deficient mice. Injection of various CRF receptor antagonists including the CRF 2 -selective antisauvagine-30 did not affect the conditioned HR response. This finding suggests that endogenous CRF does not contribute to the fear-mediated tachycardia. Thus, the hypothesis of an involvement of CRF in HR responses of mice to acute aversive stimulation is rejected. Pharmacological evidence points at the involvement of CRF 1 in enhanced sympathovagal antagonism, a pathological state contributing to elevated cardiac risk, whereas the physiological role of the brain CRF system in cardiovascular regulation remains to be determined.

A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment

“…The ECG signal was exported as a text file using Dataquest Reader (Data Sciences) and imported into Chart software (Chart 5.0, AD Instruments, Germany) for ECG data editing. Briefly, recordings were edited offline for the correction of unrecognized beats and exclusion of artifacts via the HR variability module of the Chart software as described previously (Stiedl et al 2005). Pairs of successive R waves of the ECG signal were used to derive instantaneous readings of HR, measured in beats per min (bpm).…”

5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: Implications for effects of selective serotonin reuptake inhibitors

“…These experiments followed experimental procedures described before (Tovote et al, 2004;Stiedl et al, 2005). In brief, mice were implanted with an ECG radiotransmitter (TA10EA-F20, Data Sciences, St. Paul, MN, USA) and after appropriate recovery period (2e3 weeks) subjected to a single auditory trace fear conditioning session with two presentations of tone (10 kHz, 75 dB SPL, 30 s, pulsed 5 Hz) and electric current (0.7 mA, 2 s, constant current) separated by a 15-s trace interval to involve hippocampal function (Misane et al, 2005).…”

Cognitive disruptions in stress-related psychiatric disorders: A role for corticotropin releasing factor (CRF)

“…1; Merchenthaler, 1984; Potter et al, 1994; Van Pett et al, 2000). In fact, local infusions of CRF into the periaqueductal gray increases defensive behavior, such as freezing during fear conditioning (Carvalho-Netto et al, 2007; Stiedl et al, 2005). Anatomically, CRF is also positioned to affect amygdala regions involved in the mnemonic aspects of fear conditioning (Fig.1).…”