Memory reactivation mediates emotional valence updating of contextual memory in mice with protracted morphine withdrawal.

Mice subjected to morphine locomotor sensitization develop increased anxiety-behavior expression during protracted morphine withdrawal. This behavioral change is dependent on reexposure to the context of locomotor sensitization and reflects a state of conditioned anxiety. In this study, the effect of memory reconsolidation on the expression of conditioned anxiety in mice with protracted morphine withdrawal was examined. Five experimental protocols involving male C57BL/6 mice were used in which the animals were subjected to locomotor sensitization induced by morphine and reexposed to the context associated with the drug effect 28 days after locomotor sensitization and immediately after subjected to elevated plus maze. In experiment 1, mice were subjected or not to memory reactivation session and was observed that memory reactivation 27 days after sensitization reduced conditioned anxiety. In experiment 2, mice were subjected to memory reactivation, 24 h, 6 h or 1 h before contextual reexposure, and the effect of memory reactivation coincided with the temporal requirement for reconsolidation. In experiment 3, which involved exposure to a situation of acute stress immediately before memory reactivation, the mice demonstrated a return to increased conditioned anxiety. To confirm the influence of reconsolidation, in experiments 4 and 5, mice subjected to memory reactivation were treated with Nimodipine, diazepam or cyclohexamine, substances commonly used as pharmacological controls in reconsolidation experiments. Treatment with each substance separately inhibited the effect of reactivation in experiment 5 (presence of acute stressor) but not in experiment 4 (absence of acute stressor). These results suggest that, in our experimental model, reconsolidation is mediated through updating of the emotional valence of contextual memory associated with the administration of morphine.

Overview of lymphoma diagnosis in Brazilian public health system patients: Open data analysis for health care planning

Abstract Introduction Knowing the information regarding the panorama of lymphoma diagnosis in patients treated in the Brazilian Public Unified Health System from the last 10 years is a challenge for Strategic Health Planning. Objective To characterize the Brazilian population with lymphoma treated in the Brazilian Public Unified Health System between 2008 and 2017 regarding staging, sex, residence site and mortality. Material and methods A descriptive, retrospective, and longitudinal trial with secondary data from DataSUS (SIA/SUS and SIM/SUS) obtained from patients with ICD-10 C81-85. Results There were 70,850 lymphoma cases between 2008 and 2017, of which 55% were male, the median age was 51 years, and 27% had Hodgkin Lymphoma. Most patients (56%) were treated outside the residence city. São Paulo State accounted for 25% of patients. Treatment initiation took more than 60 days in 27% of cases. A total of 45,601 deaths were due to lymphoma (12% Hodgkin Lymphoma and 88% Non-Hodgkin Lymphoma), with a median age 63 years, and were mainly males (55%). Staging data were inadequate in 23% of patients, and analysis was performed only on the valid records. Advanced disease was diagnosed in 58% of patients (60% male; 57% female) and was more common in Non-Hodgkin Lymphoma (62%) versus Hodgkin Lymphoma (49%). Discussion Late diagnosis interferes with mortality rates. Health promotion and cancer prevention campaigns, especially targeting the male public, and training for early diagnosis and early treatment are needed. Conclusion Effective measures for early diagnosis and treatment are urgently needed for lymphoma control.

Overview of lymphoma diagnosis in Brazilian public health system patients: Open data analysis for health care planning.

INTRODUCTION: Knowing the information regarding the panorama of lymphoma diagnosis in patients treated in the Brazilian Public Unified Health System from the last 10 years is a challenge for Strategic Health Planning. OBJECTIVE: To characterize the Brazilian population with lymphoma treated in the Brazilian Public Unified Health System between 2008 and 2017 regarding staging, sex, residence site and mortality. MATERIAL AND METHODS: A descriptive, retrospective, and longitudinal trial with secondary data from DataSUS (SIA/SUS and SIM/SUS) obtained from patients with ICD-10 C81-85. RESULTS: There were 70,850 lymphoma cases between 2008 and 2017, of which 55% were male, the median age was 51 years, and 27% had Hodgkin Lymphoma. Most patients (56%) were treated outside the residence city. São Paulo State accounted for 25% of patients. Treatment initiation took more than 60 days in 27% of cases. A total of 45,601 deaths were due to lymphoma (12% Hodgkin Lymphoma and 88% Non-Hodgkin Lymphoma), with a median age 63 years, and were mainly males (55%). Staging data were inadequate in 23% of patients, and analysis was performed only on the valid records. Advanced disease was diagnosed in 58% of patients (60% male; 57% female) and was more common in Non-Hodgkin Lymphoma (62%) versus Hodgkin Lymphoma (49%). DISCUSSION: Late diagnosis interferes with mortality rates. Health promotion and cancer prevention campaigns, especially targeting the male public, and training for early diagnosis and early treatment are needed. CONCLUSION: Effective measures for early diagnosis and treatment are urgently needed for lymphoma control.

Inhaled Lavandula angustifolia essential oil enhances extinction learning and inhibits memory updating in mice submitted to the contextual fear conditioning.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavender (Lavandula angustifolia) essential oil (EO) has a long history of use in emotional illness, including anxiety disorders. Cognitive mechanisms of learning and memory play a pivotal role in the etiology and maintenance of anxiety since exposure to cues related to aversive situations induces high arousal and anticipatory anxiety. Memory become labile after its reactivation and can be modulated by reconsolidation or extinction. Inhibition of memory reconsolidation or facilitation of memory extinction may be effective in preventing or minimizing the effect of contextual cues on anticipatory anxiety. AIM OF THE STUDY: We investigated the effect of Lavandula angustifolia EO in the memory updating of conditioned contextual fear. MATERIALS AND METHODS: Adult male C57Bl6 mice were submitted to fear conditioning. Two days after conditioning the mice underwent a reactivation session in a hybrid context and were then immediately exposed to vaporized water or essential oil at concentrations of 1%, 2.5% or 5% for 3 h. Two days later, the mice were tested in the original or an altered context and their freezing behavior was measured. In addition, mice were subjected to a fear memory recovery protocol followed by a reinstatement session. RESULTS: In the contextual fear test, 1% essential oil, but not 2.5% or 5%, reduced the freezing behavior response, whereas after a reinstatement session, exposure to 1% essential oil increased the freezing behavior response. CONCLUSIONS: These results suggest that Lavandula angustifolia essential oil enhances memory extinction and, consequently, inhibits memory updating.

Anxiety-like behavior in acute and protracted withdrawal after morphine-induced locomotor sensitization in C57BL/6 male mice: The role of context.

Contextual memory plays an important role in development and maintenance of drug addiction. However, little is known about of the role contextual memory in the emergence of a negative emotional state in the withdrawal period. Therefore, this study investigated anxiety-like behavior in acute and protracted morphine withdrawal of mice submitted to a locomotor sensitization protocol and the influence of contextual memory on this behavior. Male adult C57Bl6 mice were subjected to morphine locomotor sensitization and anxiety-like behavior was assessed by using the elevated plus maze test (EPM). To evaluate associative memory, the mice were re-exposed to the context of locomotor sensitization immediately before EPM. As expected, repeated morphine administrations promoted locomotor sensitization, seen as a gradual increase in the distance traveled during the acquisition phase. There was an increase in anxiety-like behavior upon acute withdrawal, as indicated by a decrease in open arms activity (OAA), but this effect dissipated over time. However, when the context was presented, mice in protracted withdrawal showed enhanced anxiety-like behavior, indicated by an increase in closed arms activity (CAA). This effect was context specific since re-exposure in an alternative context did not change the anxiety-like behavior. Treatment with diazepam counteracted the decrease in OAA in acute withdrawal and the increase in CAA induced by context re- exposure during protracted abstinence. Thus, repeated morphine administration induced a negative emotional state when the drug was discontinued. The context associated with drug exposure played a pivotal role in the appearance of anxiety-like behavior, even long after drug discontinuation. There were differences in the patterns of anxiety behaviors in acute (unconditioned anxiety-like behavior) and protracted (conditioned anxiety-like behavior) withdrawal since the former was characterized by a passive behavioral strategy and the latter by an active behavioral strategy.

Inhaled Lavandula angustifolia essential oil inhibits consolidation of contextual- but not tone-fear conditioning in rats.

Although the current treatment for anxiety is effective, it promotes a number of adverse reactions and medical interactions. Inhaled essential oils have a prominent action on the central nervous system, with minimal systemic effects, primarily because of reduced systemic bioavailability. The effects of drugs on the consolidation of fear conditioning reflects its clinical efficacy in preventing a vicious cycle of anticipatory anxiety leading to fearful cognition and anxiety symptoms. In this study, we investigated the effects of inhaled Lavandula angustifolia essential oil on the consolidation of aversive memories and its influence on c-Fos expression. Adult male Wistar rats were subjected to a fear conditioning protocol. Immediately after the training session, the rats were exposed to vaporized water or essential oil (1%, 2.5% and 5% solutions) for 4h. The next day, the rats underwent contextual- or tone-fear tests and 90min after the test they were euthanized and their brains processed for c-Fos immunohistochemistry. In the contextual-fear test, essential oil at 2.5% and 5% (but not 1%) reduced the freezing response and its respective c-Fos expression in the ventral hippocampus and amygdala. In the tone-fear test, essential oil did not reduce the freezing response during tone presentation. However, rats that inhaled essential oil at 2.5% and 5% (but not 1%) showed decreased freezing in the three minutes after tone presentation, as well as reduced c-Fos expression in the prefrontal cortex and amygdala. These results show that the inhalation of L. angustifolia essential oil inhibited the consolidation of contextual- but not tone-fear conditioning and had an anxiolytic effect in a conditioned animal model of anxiety.