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

Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: A retrospective cooperative Central-Eastern European study

Background and Objectives: Clinical experience in Western Europe suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are promising methods in the management of gastric cancer (GC) with peritoneal metastases. However, there are almost no data on such treatment results in patient from Central‐Eastern European population. Methods: A retrospective cooperative study was performed at 6 Central‐Eastern European HIPEC centers. HIPEC was used in 117 patients for the following indications: treatment of GC with limited overt peritoneal metastases (n = 70), adjuvant setting after radical gastrectomy (n = 37) and palliative approach for elimination of severe ascites without gastrectomy (n = 10). Results: Postoperative morbidity and mortality rates were 29.1% and 5.1%, respectively. Median overall survival in the groups with therapeutic, adjuvant, and palliative indications was 12.6, 34, and 3.5 months. The only long‐term survivors occurred in the group with peritoneal cancer index (PCI) of 0‐6 points without survival difference in groups with PCI 7‐12 vs PCI 13 or more points. Conclusions: GC patients with limited peritoneal metastases can benefit from CRS + HIPEC. Hyperthermic intraperitoneal chemotherapy could be an effective method of adjuvant treatment of GC with a high risk of intraperitoneal progression. No long‐term survival may be expected after palliative approach to HIPEC

Effects of gastrin-releasing peptide agonist and antagonist administered to the basolateral nucleus of the amygdala on conditioned fear in the rat

Rationale: Bombesin (BB)-like peptides have been shown to affect neuroendocrine and neural functions related to the stress response and the modulation of conditioned fear. In line with this view, central administration of gastrin-releasing peptide (GRP; a mammalian analogue of BB) or its receptor antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) BB(6-14) (RC-3095) modulates conditioned fear. Objective: The present study examined the effects of bilateral infusions of GRP or its receptor antagonist (RC-3095) into the basolateral nucleus of the amygdala (BLA) on the conditioned emotional response. Methods: The effects of GRP (150, 300, and 600 ng/0.5 microl) and/or RC-3095 (50, 500, and 1,000 ng/0.5 microl) on contextual and cued fear conditioning were assessed following direct bilateral infusion of these compounds into the BLA. Results: Both GRP and RC-3095 (all doses) reduced freezing during the contextual testing period but did not influence responding in the cued test. Although both compounds reduced freezing in the contextual paradigms, at a moderate dose pretreatment with RC-3095 attenuated the GRP-elicited decrease in contextual freezing. Conclusions: It appears that manipulation of GRP at the BLA may influence the expression of learned fear and that these effects preferentially influence contextual versus cue-dependent emotional responses