Stress Hormones Receptors in the Amygdala Mediate the Effects of Stress on the Consolidation, but Not the Retrieval, of a Non Aversive Spatial Task

This study examined the effects of the arousal level of the rat and exposure to a behavioral stressor on acquisition, consolidation and retrieval of a non-aversive hippocampal-dependent learning paradigm, the object location task. Learning was tested under two arousal conditions: no previous habituation to the experimental context (high novelty stress/arousal level) or extensive prior habituation (reduced novelty stress/arousal level). Results indicated that in the habituated rats, exposure to an out-of-context stressor (i.e, elevated platform stress) impaired consolidation and retrieval, but not acquisition, of the task. Non-habituated animals under both stressed and control conditions did not show retention of the task. In habituated rats, RU-486 (10 ng/side), a glucocorticoid receptor (GR) antagonist, or propranolol (0.75 µg/side), a beta-adrenergic antagonist, injected into the basolateral amygdala (BLA), prevented the impairing effects of the stressor on consolidation, but not on retrieval. The CB1/CB2 receptor agonist WIN55,212-2 (WIN, 5 µg/side) microinjected into the BLA did not prevent the effects of stress on either consolidation or retrieval. Taken together the results suggest that: (i) GR and β-adrenergic receptors in the BLA mediate the impairing effects of stress on the consolidation, but not the retrieval, of a neutral, non-aversive hippocampal-dependent task, (ii) the impairing effects of stress on hippocampal consolidation and retrieval are mediated by different neural mechanisms (i.e., different neurotransmitters or different brain areas), and (iii) the effects of stress on memory depend on the interaction between several main factors such as the stage of memory processing under investigation, the animal's level of arousal and the nature of the task (neutral or aversive)

Monoacylglycerol lipase inhibition-induced changes in plasma corticosterone levels, anxiety and locomotor activity in male CD1 mice

The hypothalamus-pituitary-adrenal-axis is strongly controlled by the endocannabinoid system. The specific impact of enhanced 2-arachidonoylglycerol signaling on corticosterone plasma levels, however, was not investigated so far. Here we studied the effects of the recently developed monoacylglycerol lipase inhibitor JZL184 on basal and stress-induced corticosterone levels in male CD1 mice, and found that this compound dramatically increased basal levels without affecting stress responses. Since acute changes in corticosterone levels can affect behavior, JZL184 was administered concurrently with the corticosterone synthesis inhibitor metyrapone, to investigate whether the previously shown behavioral effects of JZL184 are dependent on corticosterone. We found that in the elevated plus-maze, the effects of JZL184 on "classical" anxiety-related measures were abolished by corticosterone synthesis blockade. By contrast, effects on the "ethological" measures of anxiety (i.e. risk assessment) were not affected by metyrapone. In the open-field, the locomotion-enhancing effects of the compound were not changed either. These findings show that monoacylglycerol lipase inhibition dramatically increases basal levels of corticosterone. This endocrine effect partly affects the anxiolytic, but not the locomotion-enhancing effects of monoacylglycerol lipase blockade

The Odyssey of Dental Anxiety: From Prehistory to the Present. A Narrative Review

Dental anxiety (DA) can be considered as a universal phenomenon with a high prevalence worldwide; DA and pain are also the main causes for medical emergencies in the dental office, so their prevention is an essential part of patient safety and overall quality of care. Being DA and its consequences closely related to the fight-or-flight reaction, it seems reasonable to argue that the odyssey of DA began way back in the distant past, and has since probably evolved in parallel with the development of fight-or-flight reactions, implicit memory and knowledge, and ultimately consciousness. Basic emotions are related to survival functions in an inseparable psychosomatic unity that enable an immediate response to critical situations rather than generating knowledge, which is why many anxious patients are unaware of the cause of their anxiety. Archeological findings suggest that humans have been surprisingly skillful and knowledgeable since prehistory. Neanderthals used medicinal plants; and relics of dental tools bear witness to a kind of Neolithic proto-dentistry. In the two millennia BC, Egyptian and Greek physicians used both plants (such as papaver somniferum) and incubation (a forerunner of modern hypnosis, e.g., in the sleep temples dedicated to Asclepius) in the attempt to provide some form of therapy and painless surgery, whereas modern scientific medicine strongly understated the role of subjectivity and mind-body approaches until recently. DA has a wide range of causes and its management is far from being a matter of identifying the ideal sedative drug. A patient's proper management must include assessing his/her dental anxiety, ensuring good communications, and providing information (iatrosedation), effective local anesthesia, hypnosis, and/or a wise use of sedative drugs where necessary. Any weak link in this chain can cause avoidable suffering, mistrust, and emergencies, as well as having lifelong psychological consequences. Iatrosedation and hypnosis are no less relevant than drugs and should be considered as primary tools for the management of DA. Unlike pharmacological sedation, they allow to help patients cope with the dental procedure and also overcome their anxiety: achieving the latter may enable them to face future dental care autonomously, whereas pharmacological sedation can only afford a transient respite