Chemogenetic activation or inhibition of histaminergic neurons bidirectionally modulates recognition memory formation and retrieval in male and female mice.

Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated the effect of acute silencing or activation of histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMN neurons) in vivo in both sexes in an attempt to provide direct and causal evidence of the necessary role of these neurons in recognition memory formation and retrieval. To this end, we compared the performance of mice in two non-aversive and non-rewarded memory tests, the social and object recognition memory tasks, which are known to recruit different brain circuitries.

New β-arylchalcogeno amines with procognitive properties targeting Carbonic Anhydrases and Monoamine Oxidases.

Cognitive deficits are enduring and disabling symptoms for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. In this study, we reported the synthesis of β-arylchalcogeno amines bearing sulfurated, selenated, and tellurated moieties (2-4) which are structurally related to amphetamine with good activation properties for Carbonic Anhydrases (CAs) isoforms present in the cortical and hippocampal brain structures (hCA IV and hCA XIV). In addition, these compounds showed selective inhibition against the Monoamine oxidase (MAO) A isoform.

Modulation of Carbonic Anhydrases Activity in the Hippocampus or Prefrontal Cortex Differentially Affects Social Recognition Memory in Rats.

Growing evidence indicates that brain carbonic anhydrases (CAs) are key modulators in cognition, particularly in recognition and aversive memories. Here we described a role for these enzymes also in social recognition memory (SRM), defined as the ability to identify and recognize a conspecific, a process that is of paramount importance in gregarious species, such as rodents and humans. Male adult Wistar rats were submitted to a social discrimination task and, immediately after the sample phase, received bilateral infusions of vehicle, the CAs activator D-phenylalanine (D-Phen, 50 nmols/side), the CAs inhibitor acetazolamide (ACTZ; 10 nmols/side) or the combination of D-Phen and ACTZ directly in the CA1 region of the dorsal hippocampus or in the medial prefrontal cortex (mPFC).

Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner.

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine () and their wild type () congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress.

Oxytocin and Fear Memory Extinction: Possible Implications for the Therapy of Fear Disorders?

Several psychiatric conditions such as phobias, generalized anxiety, and post-traumatic stress disorder (PTSD) are characterized by pathological fear and anxiety. The main therapeutic approach used in the management of these disorders is exposure-based therapy, which is conceptually based upon fear extinction with the formation of a new safe memory association, allowing the reduction in behavioral conditioned fear responses. Nevertheless, this approach is only partially resolutive, since many patients have difficulty following the demanding and long process, and relapses are frequently observed over time.

Different Peas in the Same Pod: The Histaminergic Neuronal Heterogeneity.

The histaminergic neuronal system is recently receiving increasing attention, as much has been learned over the past 25 years about histamine role as a neurotransmitter. Indeed, this amine is crucial in maintaining arousal and provides important contributions to regulate circadian rhythms, energy, endocrine homeostasis, motor behavior, and cognition. The extent to which these distinct physiological functions are operated by independent histamine neuronal subpopulation is unclear.

A Duet Between Histamine and Oleoylethanolamide in the Control of Homeostatic and Cognitive Processes.

In ballet, a pas de deux (in French it means "step of two") is a duet in which the two dancers perform ballet steps together. The suite of dances shares a common theme of partnership. How could we better describe the fine interplay between oleoylethanolamide (OEA) and histamine, two phylogenetically ancient molecules controlling metabolic, homeostatic and cognitive processes? Contrary to the pas de deux though, the two dancers presumably never embrace each other as a dancing pair but execute their "virtuoso solo" constantly exchanging interoceptive messages presumably via vagal afferents, the blood stream, the neuroenteric system.

Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine.

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory.

Brain histamine and oleoylethanolamide restore behavioral deficits induced by chronic social defeat stress in mice.

The physiological mechanisms underlying the complex interplay between life stressors and metabolic factors is receiving growing interest and is being analyzed as one of the many factors contributing to depressive illness. The brain histaminergic system modulates neuronal activity extensively and we demonstrated that its integrity is necessary for peripheral signals such as the bioactive lipid mediator oleoylethanolamide (OEA) to exert its central actions. Here, we investigated the role of brain histamine and its interaction with OEA in response to chronic social defeat stress (CSDS), a preclinical protocol widely used to study physio-pathological mechanisms underlying symptoms observed in depression.

Activation of carbonic anhydrase isoforms involved in modulation of emotional memory and cognitive disorders with histamine agonists, antagonists and derivatives.

Carbonic anhydrases (CAs, EC 4.2.1.

The role of carbonic anhydrases in extinction of contextual fear memory.

Carbonic anhydrases (CAs; EC 4.2.1.

Carbonic anhydrase modulation of emotional memory. Implications for the treatment of cognitive disorders.

Carbonic anhydrases (CAs, EC 4.2.1.

Preventing adolescent stress-induced cognitive and microbiome changes by diet.

Psychological stress during adolescence may cause enduring cognitive deficits and anxiety in both humans and animals, accompanied by rearrangement of numerous brain structures and functions. A healthy diet is essential for proper brain development and maintenance of optimal cognitive functions during adulthood. Furthermore, nutritional components profoundly affect the intestinal community of microbes that may affect gut-brain communication.

Brain histamine modulates recognition memory: possible implications in major cognitive disorders.

Several behavioural tests have been developed to study and measure emotionally charged or emotionally neutral memories and how these may be affected by pharmacological, dietary or environmental manipulations. In this review, we describe the experimental paradigms used in preclinical studies to unravel the brain circuits involved in the recognition and memorization of environmentally salient stimuli devoid of strong emotional value. In particular, we focus on the modulatory role of the brain histaminergic system in the elaboration of recognition memory that is based on the judgement of the prior occurrence of an event, and it is believed to be a critical component of human declarative memory.

Neuronal histamine and the memory of emotionally salient events.

In this review, we describe the experimental paradigms used in preclinical studies to unravel the histaminergic brain circuits that modulate the formation and retrieval of memories associated with aversive events. Emotionally arousing events, especially bad ones, are remembered more accurately, clearly and for longer periods of time than neutral ones. Maladaptive elaborations of these memories may eventually constitute the basis of psychiatric disorders such as generalized anxiety, obsessive-compulsive disorders and post-traumatic stress disorder.

Histamine-deficient mice do not respond to the antidepressant-like effects of oleoylethanolamide.

It has been suggested that the bioactive lipid mediator oleoylethanolamide (OEA), a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR-α) possesses anti-depressant-like effects in several preclinical models. We recently demonstrated that several of OEA's behavioural actions require the integrity of the brain histaminergic system, and that an intact histaminergic neurotransmission is specifically required for selective serotonin re-uptake inhibitors to exert their anti-depressant-like effect. The purpose of our study was to test if OEA requires the integrity of the histaminergic neurotransmission to exert its antidepressant-like effects.

Histamine regulates memory consolidation.

Recent findings have reasserted the role of histamine in the regulation of memory consolidation first proposed in 1986 in an inhibitory avoidance task in rats. They indicate that histamine is indeed a major regulator of memory consolidation in various tasks, through H2 receptors in the dorsal hippocampus and through H3 receptors in the basolateral amygdala, depending on the task. In the object recognition task, the memory enhancing effect is mediated by the three receptors (H1, H2, H3) in the dorsal hippocampus.

Histaminergic Neurotransmission as a Gateway for the Cognitive Effect of Oleoylethanolamide in Contextual Fear Conditioning.

Background: The integrity of the brain histaminergic system is necessary for the unfolding of homeostatic and cognitive processes through the recruitment of alternative circuits with distinct temporal patterns. We recently demonstrated that the fat-sensing lipid mediator oleoylethanolamide indirectly activates histaminergic neurons to exerts its hypophagic effects. The present experiments investigated whether histaminergic neurotransmission is necessary also for the modulation of emotional memory induced by oleoylethanolamide in a contextual fear conditioning paradigm.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus.

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT).

Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/D3 antagonist sulpiride.

Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.

Donepezil, an acetylcholine esterase inhibitor, and ABT-239, a histamine H3 receptor antagonist/inverse agonist, require the integrity of brain histamine system to exert biochemical and procognitive effects in the mouse.

Histaminergic H3 receptors (H3R) antagonists enhance cognition in preclinical models and modulate neurotransmission, in particular acetylcholine (ACh) release in the cortex and hippocampus, two brain areas involved in memory processing. The cognitive deficits seen in aging and Alzheimer's disease have been associated with brain cholinergic deficits. Donepezil is one of the acetylcholinesterase (AChE) inhibitor approved for use across the full spectrum of these cognitive disorders.

The histaminergic system as a target for the prevention of obesity and metabolic syndrome.

The control of food intake and body weight is very complex. Key factors driving eating behavior are hunger and satiety that are controlled by an interplay of several central and peripheral neuroendocrine systems, environmental factors, the behavioral state and circadian rhythm, which all concur to alter homeostatic aspects of appetite and energy expenditure. Brain histamine plays a fundamental role in eating behavior as it induces loss of appetite and has long been considered a satiety signal that is released during food intake (Sakata et al.

Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus.

Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation.