Propranolol attenuates the establishment of conditioned context aversions: differential effects compared to MK-801 in an animal model of anticipatory nausea and vomiting.

Cancer patients often experience anticipatory nausea and vomiting (ANV) due to Pavlovian conditioning. Both N-methyl-D-aspartate and beta-adrenergic receptors are known to mediate memory formation, but their role in the development of ANV remains unclear. This study used a conditioned context aversion (CCA) paradigm, an animal model for ANV, to assess whether administration of the beta-adrenergic receptor antagonist propranolol or the N-methyl-D-aspartate receptor antagonist MK-801 immediately after CCA training has an effect on the later expression of CCA in CD1 male mice. In experiment 1, three groups were injected with lithium chloride (LiCl) to induce aversion in a novel context, resulting in CCA. A control group was injected with sodium chloride (NaCl). Following conditioning, two of the LiCl-treated groups received different doses of MK-801 (0.05 or 0.2 mg/kg), while the remaining LiCl-treated and NaCl-treated groups received a second NaCl injection. In experiment 2, two groups were injected with LiCl, and one group was injected with NaCl. After conditioning, one of the LiCl-treated groups received a propranolol injection (10 mg/kg). The remaining LiCl-treated and NaCl-treated groups received NaCl injections. Water consumption was measured in all groups 72 h later within the conditioning context. Postconditioning administration of propranolol, but not MK-801, attenuated CCA, as revealed by similar levels of water consumption in animals that received LiCl and propranolol relative to NaCl-treated animals. These findings suggest that beta-adrenergic receptor activation is crucial for the development of CCA. Therefore, propranolol may represent a novel therapeutic approach for cancer patients at high risk of ANV.

A pilot study examining hemomania behaviors in psychiatry outpatients engaged with nonsuicidal self-injury.

BACKGROUND: This study aims to conduct the first-ever evaluation of our previously proposed behaviors of "hemomania" in individuals engaged with nonsuicidal self-injury (NSSI). METHODS: The study encompassed 130 outpatients engaged with NSSI who applied at the psychiatry outpatient clinic. NSSI behaviors were assessed using the Inventory of Statements About Self-Injury, while psychiatric diagnoses were evaluated using the Structured Clinical Interview for DSM-5 Disorders-Clinician Version. Subsequently, participants completed the Depression Anxiety Stress Scale-21 and Short Form of Barratt Impulsiveness Scale. RESULTS: The prevalence of at least one hemomania behavior including seeing blood, tasting blood, bloodletting, and blood-drinking was observed to be 43.1% in individuals with NSSI. When participants were divided into two groups, individuals with hemomania exhibited: (1) a higher incidence of psychiatric comorbidities, increased suicide attempts, and more severe symptoms of depression, anxiety, stress, and impulsivity, (2) higher comorbidity rates of borderline personality disorder, body-focused repetitive behaviors, and dissociative disorders, and (3) elevated frequencies of certain NSSI behaviors, including cutting, biting, needle-ticking, and carving, compared to those without. CONCLUSION: Hemomania could be considered a specific impulse control disorder, characterized by heightened impulsivity and a persistent urge to obtain one's own blood. However, further studies are needed to validate this hypothesis.

Memory Impairing Effect of Propranolol on Consolidation and Reconsolidation for Various Learning Tasks.

Newly acquired memory traces have been thought to become stable and resistant to interruption after they are stored in long-term memory. However, according to a recent research drugs such as beta-adrenergic receptor antagonists enable memories to be updated and rewritten when administered during consolidation and reconsolidation. Propranolol is a widely used beta-adrenergic receptor antagonist that disrupts the consolidation and reconsolidation processes of memory formation as it inhibits protein synthesis in the central nervous system. This review aims to discuss the memory impairing effect of the systemic and intracerebral administration of propranolol during the consolidation and reconsolidation processes associated with different learning tasks. In doing so, this review will help elucidate the effects of propranolol on different stages of memory formation. Since learning and maladaptive memories underpin some of the most common psychological disorders, such as phobias, post-traumatic stress disorder, addiction, drug-seeking behavior, and so on, a thorough understanding of propranolol's memory-impairing effect has significant clinical value and the potential to help people suffering from these disorders.

Genetic and environmental influences on one-trial conditioned context aversion in mice.

Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness-inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre-exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl-induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model.