Immediate post-defeat infusions of the noradrenergic receptor antagonist propranolol impair the consolidation of conditioned defeat in male Syrian hamsters

Abstract

Summary Social defeat occurs when an animal is attacked and subjugated by an aggressive conspecific. Following social defeat, male Syrian hamsters fail to display species-typical territorial aggression and instead exhibit submissive or defensive behaviors even when in the presence of a non-aggressive intruder. We have termed this phenomenon conditioned defeat (CD). The mechanisms underlying CD are not fully understood, but data from our lab suggest that at least some of the mechanisms are similar to those that mediate classical fear conditioning. The goal of the present experiment was to test the hypothesis that noradrenergic signaling promotes the consolidation of CD, as in classical fear conditioning, by determining whether CD is disrupted by post-training blockade of noradrenergic activity. In Experiment 1, we determined whether systemic infusions of the noradrenergic receptor antagonist propranolol (0, 1.0, 10, or 20 mg/kg) given immediately after a 15 min defeat by a resident aggressor would impair CD tested 48h later. Hamsters that were given immediate post-training infusions of propranolol (1.0, but not 10 or 20 mg/kg) showed significantly less submissive behavior than those given vehicle infusions supporting the hypothesis that there is noradrenergic modulation of social defeat consolidation. In Experiment 2, we demonstrated that propranolol (1.0 mg/kg) given immediately, but not 4 or 24h, after defeat impaired CD tested 48h after defeat indicating that the window within which the memory for social defeat is susceptible to beta-adrenergic modulation is temporary. In Experiment 3, we examined whether central blockade of noradrenergic receptors could recapitulate the effect of systemic injections by giving an intracerebroventricular infusion of propranolol immediately after defeat and examining the effect on CD 24 h later. Centrally administered propranolol (20 μg/3μl but not 2 μg/3μl) was also effective in dose-dependently reducing consolidation of CD. Collectively, the present results indicate that noradrenergic activity promotes the consolidation of CD and suggest that CD is a valuable model to study the processes by which emotion and stress modulate memory in an ethologically relevant context. These data also suggest that the popular conception in the clinical literature that the anxiolytic effect of propranolol is primarily due to the drug’s peripheral effects may need to be reconsidered.

Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects

“…This effect is independent of gonadal steroids (Trainor et al, 2013) and can be reversed with chronic but not acute sertraline treatment (Greenberg et al, 2014). Male California mice exposed to defeat exhibit increased fear behavior in a resident-intruder test (Steinman et al, 2015), similar to the conditioned defeat phenotype described in Syrian hamsters (Clinard et al, 2015; Gray et al, 2015). …”

Comparing the Effects of Krebs Plus Verapamil Solution on Endothelial Function of Harvested Human Greater Saphenous Vein with Heparinized Blood, an Invitro Study

“…Thrombus then forms. This becomes the basis for later growth and development of atherosclerotic plaque and may lead to graft occlusion ( 24 , 25 ). There are various types of solution used for storing conduits before anastomosis ( 25 ).…”

“…This becomes the basis for later growth and development of atherosclerotic plaque and may lead to graft occlusion ( 24 , 25 ). There are various types of solution used for storing conduits before anastomosis ( 25 ). Verapamil is a Ca2+ channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug ( 25 ).…”

“…There are various types of solution used for storing conduits before anastomosis ( 25 ). Verapamil is a Ca2+ channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug ( 25 ). In our study, 4 different solutions were used for preserving 3 mm rings of saphenous veins compare with autologous heparinized whole blood as normal storage solution in operation rooms.…”

“…Guo-Wei He showed that using verapamil + nitroglycerin solution for preparing radial artery can maximally preserves endothelial function in contrast to papaverine. verapamil + nitroglycerin solution may be effectively and safely used to prepare the radial artery for coronary artery bypass grafting( 25 , 26 ). P. DI.…”