Enhanced Fear Expression in a Psychopathological Mouse Model of Trait Anxiety: Pharmacological Interventions

The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α2,3,5-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias

Analysis of the semileptonic Bc→D10B_c\rightarrow D_1^0 B c → D 1 0 transition in QCD sum rules and HQET

We investigate the structure of the $$D_{1}^0(2420[2430])(J^P=1^+)$$ mesons via analyzing the semileptonic $$B_{c}\rightarrow D_{1}^0 l\nu$$ transition in the frame work of the three-point QCD sum rules and the heavy-quark effective theory. We consider the $$D_{1}^0$$ meson in three ways: as a pure $$|c\bar{u}\rangle$$ state, as a mixture of the two $$|^3P_1\rangle$$ and $$|^1P_1\rangle$$ states with a mixing angle $$\theta$$, and as a combination of the two mentioned states with mixing angle $$\theta =35.3^\circ$$ in the heavy-quark limit. Taking into account the gluon condensate contributions, the relevant form factors are obtained for the three above conditions. These form factors are numerically calculated for $$|c\bar{u}\rangle$$ and the heavy-quark limit cases. The obtained results for the form factors are used to evaluate the decay rates and the branching ratios. Also for mixed states, all of the mentioned physical quantities are plotted with respect to the unknown mixing angle $$\theta$$

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Oxytocin reportedly decreases anxious feelings in humans and may therefore have therapeutic value for anxiety disorders, such as post-traumatic stress disorder (PTSD). As PTSD patients have exaggerated startle responses, a fear-potentiated startle paradigm in rats may have face validity as an animal model to examine the efficacy of oxytocin in treating these symptoms. Oxytocin (0, 0.01, 0.1, or 1.0 μg, subcutaneously) was given either 30 min before fear conditioning, immediately after fear conditioning, or 30 min before fear-potentiated startle testing to assess its effects on acquisition, consolidation, and expression of conditioned fear, respectively. Startle both in the presence and absence of the fear-conditioned light was significantly diminished by oxytocin when administered at acquisition, consolidation, or expression. There was no specific effect of oxytocin on light fear-potentiated startle. In an additional experiment, oxytocin had no effects on acoustic startle without previous fear conditioning. Further, in a context-conditioned test, previous light-shock fear conditioning did not increase acoustic startle during testing when the fear-conditioned light was not presented. The data suggest that oxytocin did not diminish cue-specific conditioned nor contextually conditioned fear, but reduced background anxiety. This suggests that oxytocin has unique effects of decreasing background anxiety without affecting learning and memory of a specific traumatic event. Oxytocin may have antianxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in PTSD patients