Explore the vast range of titles available.

Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation. Significance An involvement of exogenous cannabinoids in the regulation of memory for emotional events has emerged over the past decade. The present findings demonstrate that after an aversive training experience the endogenous cannabinoid anandamide is released into the amygdala, hippocampus, and medial prefrontal cortex (mPFC) and normally plays a role in the formation of a strong memory trace. Furthermore, an intact basolateral amygdala is required to coordinate both hippocampal and mPFC endocannabinoid activity during aversive memory consolidation. Thus, our findings provide the first evidence, to our knowledge, that a dynamic network involving anandamide signaling within this prefrontal-limbic circuit modulates the consolidation of memory for emotionally arousing training.

Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, the present experiments investigated whether the endocannabinoid system in the BLA influences memory consolidation and whether glucocorticoids interact with this system. The CB1 receptor agonist WIN55,212-2 (5-50 ng per 0.2 μL per side), infused bilaterally into the BLA of male Sprague-Dawley rats immediately after inhibitory avoidance training, induced dose-dependent enhancement of 48-h retention. Conversely, the CB1 receptor antagonist AM251 (0.07-0.28 ng per 0.2 μL per side) administered after training into the BLA induced inhibitory avoidance retention impairment. Furthermore, intra-BLA infusions of a low and nonimpairing dose of AM251 (0.14 ng per 0.2 μL per side) blocked the memory enhancement induced by concurrent administration of WIN55,212-2. Delayed infusions of WIN55,212-2 or AM251 administered into the BLA 3 h after training or immediate posttraining infusions of these drugs into the adjacent central amygdala did not significantly alter retention performance. Last, intra-BLA infusions of a low and otherwise nonimpairing dose of AM251 (0.14 ng per 0.2 μL per side) blocked the memory-enhancing effect induced by systemic administration of corticosterone (3 mg/kg, s.c.). These findings indicate that endocannabinoids in the BLA enhance memory consolidation and suggest that CB1 activity within this brain region is required for enabling glucocorticoid effects on memory consolidation enhancement.

Over the last few years, several preclinical studies have shown that some herbal products, such as ferulic acid, Ginkgo biloba , and resveratrol, exert neuroprotective effects through the modulation of the heme oxygenase/biliverdin reductase system. Unfortunately, sufficient data supporting the shift of knowledge from preclinical studies to humans, particularly in neurodegenerative diseases, are not yet available in the literature. The purpose of this review is to summarize the studies and the main results achieved on the potential therapeutic role of the interaction between the heme oxygenase/biliverdin reductase system with ferulic acid, G. biloba , and resveratrol. Some critical issues have also been reported, mainly concerning the safety profile and the toxicological sequelae associated to the supplementation with the herbs mentioned above, based on both current literature and specific reports issued by the competent Regulatory Authorities.

Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long-term retention of object recognition memory.

The ability to remember contexts associated with aversive and rewarding experiences provides a clear adaptive advantage to animals foraging in the wild. The present experiments investigated whether hormonal signals released during feeding might enhance memory of recently experienced contextual information. Oleoylethanolamide (OEA) is an endogenous lipid mediator that is released when dietary fat enters the small intestine. OEA mediates fat-induced satiety by engaging type-α peroxisome proliferator-activated receptors (PPAR-α) in the gut and recruiting local afferents of the vagus nerve. Here we show that post-training administration of OEA in rats improves retention in the inhibitory avoidance and Morris water maze tasks. These effects are blocked by infusions of lidocaine into the nucleus tractus solitarii (NTS) and by propranolol infused into the basolateral complex of the amygdala (BLA). These findings suggest that the memory-enhancing signal generated by OEA activates the brain via afferent autonomic fibers and stimulates noradrenergic transmission in the BLA. The actions of OEA are mimicked by PPAR-α agonists and abolished in mutant mice lacking PPAR-α. The results indicate that OEA, acting as a PPAR-α agonist, facilitates memory consolidation through noradrenergic activation of the BLA, a mechanism that is also critically involved in memory enhancement induced by emotional arousal.

The psychoactive constituent of cannabis, Δ 9 -tetrahydrocannabinol, produces in humans subjective responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabinoids may contribute to the control of emotion. But the variable effects of Δ 9 -tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic potential of direct cannabinoid agonists. An alternative approach may be to develop drugs that amplify the effects of endogenous cannabinoids by preventing their inactivation. Here we describe a class of potent, selective and systemically active inhibitors of fatty acid amide hydrolase, the enzyme responsible for the degradation of the endogenous cannabinoid anandamide. Like clinically used anti-anxiety drugs, in rats the inhibitors exhibit benzodiazepine-like properties in the elevated zero-maze test and suppress isolation-induced vocalizations. These effects are accompanied by augmented brain levels of anandamide and are prevented by CB1 receptor blockade. Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.

Social play behavior is a highly rewarding, developmentally important form of social interaction in young mammals. However, its neurobiological underpinnings remain incompletely understood. Previous work has suggested that opioid and endocannabinoid neurotransmission interact in the modulation of social play. Therefore, we combined behavioral, pharmacological, electrophysiological, and genetic approaches to elucidate the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid neurotransmission interact to control social behavior in adolescent rodents. Systemic administration of the 2-AG hydrolysis inhibitor JZL184 or the opioid receptor agonist morphine increased social play behavior in adolescent rats. These effects were blocked by systemic pretreatment with either CB1 cannabinoid receptor (CB1R) or mu-opioid receptor (MOR) antagonists. The social play-enhancing effects of systemic morphine or JZL184 treatment were also prevented by direct infusion of the CB1R antagonist SR141716 and the MOR antagonist naloxone into the nucleus accumbens core (NAcC). Searching for synaptic correlates of these effects in adolescent NAcC excitatory synapses, we observed that CB1R antagonism blocked the effect of the MOR agonist DAMGO and, conversely, that naloxone reduced the effect of a cannabinoid agonist. These results were recapitulated in mice, and completely abolished in CB1R and MOR knockout mice, suggesting that the functional interaction between CB1R and MOR in the NAcC in the modulation of social behavior is widespread in rodents. The data shed new light on the mechanism by which endocannabinoid lipids and opioid peptides interact to orchestrate rodent socioemotional behaviors.

This work presents the first results obtained by applying in situ and remote-sensing methodologies to monitor the Ponte della Musica-Armando Trovajoli located in Rome, within the activities of the WP6 “Structural Health Monitoring and Satellite Data” 2019-21 Reluis Project. In particular, the use of remote-sensing Differential Synthetic Aperture Radar (SAR) Interferometry (DInSAR) measurements provided a spatial map of the displacement of the investigated infrastructure and the corresponding time-series, with the aim of monitoring deformation phenomena, focusing on the local scale analysis, which produces suitable results for urban monitoring and damage assessment. The DInSAR results have been integrated with the identification of the dynamic characteristics of the bridge, performed through an experimental campaign of ambient vibration measurements carried out in October 2020 and with the local-scale definition of the engineering geological setting of the foundation soil. The subsoil of the bridge is constituted by more than 50 m of recent alluvial deposits resting on Pliocene stiff clay acting as a geological bedrock. A substantially stable behavior of the bridge structural elements has been observed based on the analysis of both satellite and velocimetric data. This case represents a good example about how the integration of in situ sensors with remotely sensed data and the exploitation of a detailed knowledge regarding the on-site conditions represent a key factor for a sustainable structural and infrastructural monitoring and can support the planning both of maintenance and safety management.

The endocannabinoids anandamide and 2-arachidonoyglycerol (2-AG) may contribute to the regulation of mood and emotion. In this study, we investigated the impact of the endocannabinoid transport inhibitor AM404 on three rat models of anxiety: elevated plus maze, defensive withdrawal and separation-induced ultrasonic vocalizations. AM404 (1-5 mg kg(-1), intraperitoneal (i.p.)) exerted dose-dependent anxiolytic-like effects in the three models. These behavioral effects were associated with increased levels of anandamide, but not 2-AG, in the prefrontal cortex and were prevented by the CB(1) cannabinoid antagonist rimonabant (SR141716A), suggesting that they were dependent on anandamide-mediated activation of CB(1) cannabinoid receptors. We also evaluated whether AM404 might influence motivation (in the conditioned place preference (CPP) test), sensory reactivity (acoustic startle reflex) and sensorimotor gating (prepulse inhibition (PPI) of the startle reflex). In the CPP test, AM404 (1.25-10 mg kg(-1), i.p.) elicited rewarding effects in rats housed under enriched conditions, but not in rats kept in standard cages. Moreover, AM404 did not alter reactivity to sensory stimuli or cause overt perceptual distortion, as suggested by its lack of effect on startle or PPI of startle. These results support a role of anandamide in the regulation of emotion and point to the anandamide transport system as a potential target for anxiolytic drugs.

It has been suggested that endocannabinoid mechanisms are involved in the control of ethanol consumption. The aims of the present study were (1) to evaluate the role of the endocannabinoid system in the control of operant ethanol self-administration and in the reinstatement of ethanol seeking, when induced by stress or conditioned stimuli and (2) to offer new insights on the specificity of such a role. Rats were administered intraperitoneally with the selective cannabinoid CB1 receptor antagonist, SR-141716A, 30 min before operant self-administration or reinstatement sessions. Two schedules of reinforcement, the fixed-ratio 1 (FR1) and the progressive ratio (PR), were used to study 10% (w/v) alcohol and 5.0% sucrose self-administration. NaCl (2% w/v) intake in sodium-depleted rats was studied only under the FR1 program. Treatment with SR-141716A (0.3-3.0 mg/kg) significantly attenuated FR1 alcohol self-administration and lowered the break point for ethanol under PR. SR-141716A also markedly inhibited the reinstatement of alcohol seeking elicited by presentation of cues predictive of drug availability. Conversely, the cannabinoid antagonist did not prevent the reinstatement of alcohol seeking induced by foot-shock stress. Lever pressing for sucrose under FR1 and PR schedules was also significantly decreased by SR-141716A treatment, whereas the drug modestly and only at the highest dose decreased 2% NaCl self-administration. Results emphasize that endocannabinoid mechanisms play a major role in the control of ethanol self-administration and in the reinstatement of conditioned ethanol seeking. However, these effects extend to the control of operant behaviours motivated by natural rewards (i.e. sucrose). On the other hand, SR-141716A only weakly reduces NaCl self-administration in sodium-depleted rats, in which salt intake is largely controlled by homeostatic mechanisms. Overall, these observations demonstrate that the inhibition of operant behaviour following blockade of CB1 receptors by SR-141716A is linked to a reduction of reward-related responding and is not related to drug-induced motor deficits.